Scholars@Duke
W Daniel Stamer

W Daniel Stamer

Joseph A.C. Wadsworth Distinguished Professor of Ophthalmology
Ophthalmology, Glaucoma
william.stamer@duke.edu
Duke Eye Center, DUMC 3802, Aeri 4th Floor, Durham, NC 27710
DUMC 3802, Durham, NC 27710

Selected Publications

A Comprehensive Protocol for Microbead-Induced Ocular Hypertension in Mice.

Journal Article Methods Mol Biol · 2025 Glaucoma is a common optic neuropathy characterized by degeneration of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP), that is, ocular hypertension, is the primary modifiable risk factor for glaucoma and the primary characteristic of mo ... Full text Link to item Cite

Small Extracellular Vesicle-Associated MiRNAs in Polarized Retinal Pigmented Epithelium.

Journal Article Invest Ophthalmol Vis Sci · November 4, 2024 PURPOSE: Oxidative stress in the retinal pigmented epithelium (RPE) has been implicated in age-related macular degeneration by impacting endocytic trafficking, including the formation, content, and secretion of extracellular vesicles (EVs). Using our model ... Full text Open Access Link to item Cite

Transcriptomic profiling of Schlemm's canal cells reveals a lymphatic-biased identity and three major cell states.

Journal Article Elife · October 18, 2024 Schlemm's canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemm's canal endothelial cells (SECs) with different morphologies and functions. Recent transc ... Full text Link to item Cite

Transcriptomic profiling of Schlemm's canal cells reveals a lymphatic-biased identity and three major cell states.

Journal Article bioRxiv · August 6, 2024 Schlemm's canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemm's canal endothelial cells (SECs) with different morphologies and functions. Recent transc ... Full text Link to item Cite

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway.

Journal Article J Biomech Eng · August 1, 2024 Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intra-ocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate lig ... Full text Link to item Cite

TRPV4 and chloride channels mediate volume sensing in trabecular meshwork cells.

Journal Article Am J Physiol Cell Physiol · August 1, 2024 Aqueous humor drainage from the anterior eye determines intraocular pressure (IOP) under homeostatic and pathological conditions. Swelling of the trabecular meshwork (TM) alters its flow resistance but the mechanisms that sense and transduce osmotic gradie ... Full text Link to item Cite

Aging and intraocular pressure homeostasis in mice.

Journal Article Aging Cell · July 2024 Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues ... Full text Link to item Cite

The Factors Affecting the Stability of IOP Homeostasis.

Journal Article Invest Ophthalmol Vis Sci · June 3, 2024 PURPOSE: Shear-induced nitric oxide (NO) production by Schlemm's canal (SC) endothelial cells provides a fast, IOP-sensitive feedback signal that normally contributes to IOP homeostasis. Our goal was to analyze the response of this homeostatic system under ... Full text Link to item Cite

The JOPT Story: 40 Years of Growth and Focus.

Journal Article J Ocul Pharmacol Ther · April 2024 Full text Link to item Cite

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway.

Journal Article bioRxiv · March 25, 2024 Murine models are commonly used to study glaucoma, the leading cause of irreversible blindness. Glaucoma is associated with elevated intraocular pressure (IOP), which is regulated by the tissues of the aqueous outflow pathway. In particular, pectinate liga ... Full text Link to item Cite

ANGPTL7 and Its Role in IOP and Glaucoma.

Journal Article Invest Ophthalmol Vis Sci · March 5, 2024 PURPOSE: Loss-of-function variants in the ANGPTL7 gene are associated with protection from glaucoma and reduced intraocular pressure (IOP). We investigated the role of ANGPTL7 in IOP homeostasis and its potential as a target for glaucoma therapeutics. METH ... Full text Link to item Cite

Targeting YAP/TAZ mechanosignaling to ameliorate stiffness-induced Schlemm's canal cell pathobiology.

Journal Article Am J Physiol Cell Physiol · February 1, 2024 Pathological alterations in the biomechanical properties of the Schlemm's canal (SC) inner wall endothelium and its immediate vicinity are strongly associated with ocular hypertension in glaucoma due to decreased outflow facility. Specifically, the underly ... Full text Link to item Cite

Aging and intraocular pressure homeostasis in mice.

Journal Article bioRxiv · December 7, 2023 Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues ... Full text Link to item Cite

Estrogen dysregulation, intraocular pressure, and glaucoma risk.

Journal Article Exp Eye Res · December 2023 Characterized by optic nerve atrophy due to retinal ganglion cell (RGC) death, glaucoma is the leading cause of irreversible blindness worldwide. Of the major risk factors for glaucoma (age, ocular hypertension, and genetics), only elevated intraocular pre ... Full text Link to item Cite

Development and testing of a metabolic chamber for effluent collection during whole eye perfusions.

Journal Article Exp Eye Res · November 2023 Ocular hypertension is caused by dysregulated outflow resistance regulation by the conventional outflow (CO) pathway. The physiology of the CO pathway can be directly studied during ex vivo ocular perfusions. In addition to measuring outflow resistance gen ... Full text Link to item Cite

Genetic background determines severity of Loxl1-mediated systemic and ocular elastosis in mice.

Journal Article Dis Model Mech · November 1, 2023 Pseudoexfoliation syndrome (PEX) is a systemic, age-related disorder characterized by elastosis and extracellular matrix deposits. Its most significant ocular manifestation is an aggressive form of glaucoma associated with variants in the gene encoding lys ... Full text Link to item Cite

Lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) lncRNA differentially regulates gene and protein expression, signaling and morphology of human ocular cells.

Journal Article Hum Mol Genet · October 17, 2023 Pseudoexfoliation glaucoma (PEXG) is characterized by dysregulated extracellular matrix (ECM) homeostasis that disrupts conventional outflow function and increases intraocular pressure (IOP). Prolonged IOP elevation results in optic nerve head damage and v ... Full text Open Access Link to item Cite

Polarized Desmosome and Hemidesmosome Shedding via Small Extracellular Vesicles is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.

Journal Article J Extracell Biol · October 2023 The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age- ... Full text Link to item Cite

Targeting YAP mechanosignaling to ameliorate stiffness-induced Schlemm's canal cell pathobiology.

Journal Article bioRxiv · September 9, 2023 Pathologic alterations in the biomechanical properties of the Schlemm's canal (SC) inner wall endothelium and its immediate vicinity are strongly associated with ocular hypertension in glaucoma due to decreased outflow facility. Specifically, the underlyin ... Full text Link to item Cite

Differential roles of FOXC2 in the trabecular meshwork and Schlemm's canal in glaucomatous pathology.

Journal Article Life Sci Alliance · September 2023 Impaired development and maintenance of Schlemm's canal (SC) are associated with perturbed aqueous humor outflow and intraocular pressure. The angiopoietin (ANGPT)/TIE2 signaling pathway regulates SC development and maintenance, whereas the molecular mecha ... Full text Link to item Cite

Regulatory Effects of GPR158 Overexpression in Trabecular Meshwork Cells of the Eye’s Aqueous Outflow Pathways

Journal Article Stresses · September 1, 2023 Elevated intraocular pressure (IOP), the major risk factor for glaucoma, is caused by decreased outflow through the trabecular meshwork (TM). The pathophysiology of ocular hypertension has been linked to stress pathways, including fibrosis, calcification a ... Full text Cite

Rare protective variants and glaucoma-relevant cell stressors modulate Angiopoietin-like 7 expression.

Journal Article Hum Mol Genet · July 20, 2023 Rare missense and nonsense variants in the Angiopoietin-like 7 (ANGPTL7) gene confer protection from primary open-angle glaucoma (POAG), though the functional mechanism remains uncharacterized. Interestingly, a larger variant effect size strongly correlate ... Full text Link to item Cite

Polarized Desmosome and Hemidesmosome Shedding via Exosomes is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.

Journal Article bioRxiv · June 13, 2023 The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age- ... Full text Link to item Cite

Pressure Clamping During Ocular Perfusions Drives Nitric Oxide-Mediated Washout.

Journal Article Invest Ophthalmol Vis Sci · June 1, 2023 PURPOSE: The aim of this study was to test the hypothesis that nitric oxide (NO) mediates a pressure-dependent, negative feedback loop that maintains conventional outflow homeostasis and thus IOP. If true, holding pressure during ocular perfusions will res ... Full text Link to item Cite

Proposed Mechanism of Long-Term Intraocular Pressure Lowering With the Bimatoprost Implant.

Journal Article Invest Ophthalmol Vis Sci · March 1, 2023 PURPOSE: The purpose of this study was to evaluate the effects of pharmacologically relevant bimatoprost and bimatoprost free acid (BFA) concentrations on matrix metalloproteinase (MMP) gene expression in cells from human aqueous outflow tissues. METHODS: ... Full text Link to item Cite

Differences in Outflow Facility Between Angiographically Identified High- Versus Low-Flow Regions of the Conventional Outflow Pathways in Porcine Eyes.

Journal Article Invest Ophthalmol Vis Sci · March 1, 2023 PURPOSE: To investigate differences in outflow facility between angiographically determined high- and low-flow segments of the conventional outflow pathway in porcine eyes. METHODS: Porcine anterior segments (n = 14) were mounted in a perfusion chamber and ... Full text Link to item Cite

Greater Outflow Facility Increase After Targeted Trabecular Bypass in Angiographically Determined Low-low Regions.

Journal Article Ophthalmol Glaucoma · 2023 PURPOSE: To investigate the impact of trabecular bypass surgery targeted to angiographically determined high- vs. low-aqueous humor outflow areas on outflow facility (C) and intraocular pressure (IOP). DESIGN: Ex vivo comparative study. SUBJECTS: Postmorte ... Full text Link to item Cite

Shear stress induces autophagy in Schlemm's canal cells via primary cilia-mediated SMAD2/3 signaling pathway.

Journal Article Autophagy Rep · 2023 The Schlemm's canal (SC) is a circular, lymphatic-like vessel located at the limbus of the eye that participates in the regulation of aqueous humor drainage to control intraocular pressure (IOP). Circumferential flow of aqueous humor within the SC lumen ge ... Full text Link to item Cite

Development of a Schlemm's Canal "Inner Wall on a Chip" for High Content Screening

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2023 Cite

TRPV4 regulates cytoskeletal and extracellular matrix remodeling in Schlemm's canal cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2023 Cite

Artificial Intelligence Models for Cell Type and Subtype Identification Based on Single-Cell RNA Sequencing Data in Vision Science.

Journal Article IEEE/ACM Trans Comput Biol Bioinform · 2023 Single-cell RNA sequencing (scRNA-seq) provides a high throughput, quantitative and unbiased framework for scientists in many research fields to identify and characterize cell types within heterogeneous cell populations from various tissues. However, scRNA ... Full text Link to item Cite

Tissue Resident Macrophages in Trabecular Meshwork Contribute to Outflow Homeostasis

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2023 Cite

LOXL1 modulates TGFβ1-induced fibrosis in conventional outflow cells/tissues

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2023 Cite

Pressure clamping during ocular perfusions drives nitric oxide-mediated washout

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2023 Cite

Comparison of the extracellular vesicle proteome between glaucoma and non-glaucoma trabecular meshwork cells.

Journal Article Front Ophthalmol (Lausanne) · 2023 INTRODUCTION: Extracellular matrix (ECM) materials accumulate in the trabecular meshwork (TM) tissue of patients with glaucoma, which is associated with a decrease in aqueous humor outflow and therefore an increase in intraocular pressure. To explore a pot ... Full text Link to item Cite

Decreased outflow facility and Schlemm's canal defects in a mouse model of glaucoma.

Journal Article Exp Eye Res · December 2022 Previously we identified B6.EDA+/+ mice as a novel mouse model that presents with elevated IOP and trabecular meshwork damage. Here, we expand on our previous findings by measuring aqueous humor outflow facility and analyzing the integrity of the inner wal ... Full text Link to item Cite

Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease.

Journal Article Prog Retin Eye Res · November 2022 Caveolae, specialized plasma membrane invaginations present in most cell types, play important roles in multiple cellular processes including cell signaling, lipid uptake and metabolism, endocytosis and mechanotransduction. They are found in almost all cel ... Full text Link to item Cite

YAP/TAZ Mediate TGFβ2-Induced Schlemm's Canal Cell Dysfunction.

Journal Article Investigative ophthalmology & visual science · November 2022 PurposeElevated transforming growth factor beta2 (TGFβ2) levels in the aqueous humor have been linked to glaucomatous outflow tissue dysfunction. Potential mediators of dysfunction are the transcriptional coactivators, Yes-associated protein (YAP) ... Full text Cite

A novel glaucoma approach: Stem cell regeneration of the trabecular meshwork.

Journal Article Prog Retin Eye Res · September 2022 Glaucoma is the leading cause of global irreversible blindness, necessitating research for new, more efficacious treatment options than currently exist. Trabecular meshwork (TM) cells play an important role in the maintenance and function of the aqueous ou ... Full text Link to item Cite

Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure.

Journal Article Int J Mol Sci · July 1, 2022 Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive extracellular matrix (ECM) deposition. ... Full text Link to item Cite

The role of microRNAs in glaucoma.

Journal Article Exp Eye Res · February 2022 In this review, we aim to provide a comprehensive summary of the various microRNAs (miRNAs) shown to be involved in glaucoma and intraocular pressure regulation. miRNAs are short, single-stranded, and noncoding RNAs that regulate gene expression in a numbe ... Full text Link to item Cite

Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.

Journal Article Invest Ophthalmol Vis Sci · February 1, 2022 Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are cr ... Full text Link to item Cite

Matrix Mechanotransduction via Yes-Associated Protein in Human Lamina Cribrosa Cells in Glaucoma.

Journal Article Invest Ophthalmol Vis Sci · January 3, 2022 PURPOSE: Extracellular matrix stiffening is characteristic of both aging and glaucoma, and acts as a promoter and perpetuator of pathological fibrotic remodeling. Here, we investigate the role of a mechanosensitive transcriptional coactivator, Yes-associat ... Full text Link to item Cite

Anterior Segment Anatomy and Conventional Outflow Physiology of the Tree Shrew (Tupaia belangeri).

Journal Article Invest Ophthalmol Vis Sci · January 3, 2022 PURPOSE: Rodent and primate models are commonly used in glaucoma research; however, both have their limitations. The tree shrew (Tupaia belangeri) is an emerging animal model for glaucoma research owing in part to having a human-like optic nerve head anato ... Full text Link to item Cite

Open-source deep learning-based automatic segmentation of mouse Schlemm's canal in optical coherence tomography images.

Journal Article Exp Eye Res · January 2022 The purpose of this study was to develop an automatic deep learning-based approach and corresponding free, open-source software to perform segmentation of the Schlemm's canal (SC) lumen in optical coherence tomography (OCT) scans of living mouse eyes. A no ... Full text Link to item Cite

Extracellular Matrix Stiffness and TGFβ2 Regulate YAP/TAZ Activity in Human Trabecular Meshwork Cells.

Journal Article Front Cell Dev Biol · 2022 Primary open-angle glaucoma progression is associated with increased human trabecular meshwork (HTM) stiffness and elevated transforming growth factor beta 2 (TGFβ2) levels in the aqueous humor. Increased transcriptional activity of Yes-associated protein ... Full text Link to item Cite

A Role of Caveolae in Trabecular Meshwork Mechanosensing and Contractile Tone.

Journal Article Front Cell Dev Biol · 2022 Polymorphisms in the CAV1/2 gene loci impart increased risk for primary open-angle glaucoma (POAG). CAV1 encodes caveolin-1 (Cav1), which is required for biosynthesis of plasma membrane invaginations called caveolae. Cav1 knockout mice exhibit elevated int ... Full text Link to item Cite

Outflow segmentation patterns and pilocarpine induced outflow changes with age

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2022 Cite

The regulatory role of LOXL1-AS1 in gene expression

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2022 Cite

Cellular Mechanisms Regulating Conventional Outflow of Aqueous Humor

Chapter · January 1, 2022 Despite its small size, the trabecular meshwork (TM, including the inner wall of Schlemm's canal) is functionally complex, containing multiple cell "types" segregated by location and playing a central role in intraocular pressure (IOP) homeostasis. TM cell ... Full text Cite

Glaucomatous stressors drive Schlemm's canal cell pathobiology via elevated YAP activity

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2022 Cite

Thrombospondin-1 mediates Rho-kinase inhibitor-induced increase in outflow-facility.

Journal Article J Cell Physiol · December 2021 Rho-kinase (ROCK) inhibitors, a novel class of anti-glaucoma agents, act by increasing the aqueous humor outflow through the conventional trabecular meshwork pathway. However, the downstream signaling consequences of the ROCK inhibitor are not completely u ... Full text Link to item Cite

Identification of Estrogen Signaling in a Prioritization Study of Intraocular Pressure-Associated Genes.

Journal Article Int J Mol Sci · September 24, 2021 Elevated intraocular pressure (IOP) is the only modifiable risk factor for primary open-angle glaucoma (POAG). Herein we sought to prioritize a set of previously identified IOP-associated genes using novel and previously published datasets. We identified s ... Full text Link to item Cite

Fibrotic Changes to Schlemm's Canal Endothelial Cells in Glaucoma.

Journal Article Int J Mol Sci · August 31, 2021 Previous studies have shown that glaucomatous Schlemm's canal endothelial cells (gSCECs) are stiffer and associated with reduced porosity and increased extracellular matrix (ECM) material compared to SCECs from healthy individuals. We hypothesised that Sch ... Full text Link to item Cite

Surface Engineering of FLT4-Targeted Nanocarriers Enhances Cell-Softening Glaucoma Therapy.

Journal Article ACS Appl Mater Interfaces · July 21, 2021 Primary open-angle glaucoma is associated with elevated intraocular pressure (IOP) that damages the optic nerve and leads to gradual vision loss. Several agents that reduce the stiffness of pressure-regulating Schlemm's canal (SC) endothelial cells, in the ... Full text Link to item Cite

The vital role for nitric oxide in intraocular pressure homeostasis.

Journal Article Prog Retin Eye Res · July 2021 Catalyzed by endothelial nitric oxide (NO) synthase (eNOS) activity, NO is a gaseous signaling molecule maintaining endothelial and cardiovascular homeostasis. Principally, NO regulates the contractility of vascular smooth muscle cells and permeability of ... Full text Link to item Cite

Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy.

Journal Article Pharmaceutics · June 17, 2021 In glaucoma therapy, nanoparticles (NPs) are a favorable tool for delivering drugs to the outflow tissues of the anterior chamber of the eye where disease development and progression take place. In this context, a prerequisite is an efficient enrichment of ... Full text Link to item Cite

Optogenetic Modulation of Intraocular Pressure in a Glucocorticoid-Induced Ocular Hypertension Mouse Model.

Journal Article Transl Vis Sci Technol · May 3, 2021 PURPOSE: Steroid-induced glaucoma is a common form of secondary open angle glaucoma characterized by ocular hypertension (elevated intraocular pressure [IOP]) in response to prolonged glucocorticoid exposure. Elevated IOP occurs with increased outflow resi ... Full text Link to item Cite

The ocular pulse decreases aqueous humor outflow resistance by stimulating nitric oxide production.

Journal Article Am J Physiol Cell Physiol · April 1, 2021 Intraocular pressure (IOP) is not static, but rather oscillates by 2-3 mmHg because of cardiac pulsations in ocular blood volume known as the ocular pulse. The ocular pulse induces pulsatile shear stress in Schlemm's canal (SC). We hypothesize that the ocu ... Full text Link to item Cite

A tissue-engineered human trabecular meshwork hydrogel for advanced glaucoma disease modeling.

Journal Article Exp Eye Res · April 2021 Abnormal human trabecular meshwork (HTM) cell function and extracellular matrix (ECM) remodeling contribute to HTM stiffening in primary open-angle glaucoma (POAG). Most current cellular HTM model systems do not sufficiently replicate the complex native th ... Full text Link to item Cite

Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis.

Journal Article Elife · March 30, 2021 Glucocorticoids are widely used as an ophthalmic medication. A common, sight-threatening adverse event of glucocorticoid usage is ocular hypertension, caused by dysfunction of the conventional outflow pathway. We report that netarsudil, a rho-kinase inhibi ... Full text Link to item Cite

siRNA targeting Schlemm's canal endothelial tight junctions enhances outflow facility and reduces IOP in a steroid-induced OHT rodent model.

Journal Article Mol Ther Methods Clin Dev · March 12, 2021 Systemic or localized application of glucocorticoids (GCs) can lead to iatrogenic ocular hypertension, which is a leading cause of secondary open-angle glaucoma and visual impairment. Previous work has shown that dexamethasone increases zonula occludens-1 ... Full text Link to item Cite

Piezo1 channels mediate trabecular meshwork mechanotransduction and promote aqueous fluid outflow.

Journal Article J Physiol · January 2021 KEY POINTS: Trabecular meshwork (TM) is a highly mechanosensitive tissue in the eye that regulates intraocular pressure through the control of aqueous humour drainage. Its dysfunction underlies the progression of glaucoma but neither the mechanisms through ... Full text Link to item Cite

In vivo estimation of murine iris stiffness using finite element modeling.

Journal Article Exp Eye Res · January 2021 The iris plays an important role in certain types of glaucoma, including primary angle-closure glaucoma and pigmentary glaucoma. Iris mechanics are also important in influencing trabecular meshwork deformation in response to intraocular pressure changes in ... Full text Link to item Cite

Macrophage Ontogeny and Distribution within the Conventional Outflow Tract

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2021 Cite

Identification of ESR1 in aqueous humor outflow pathway tissues

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · 2021 Cite

A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure.

Journal Article Invest Ophthalmol Vis Sci · December 1, 2020 PURPOSE: Tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) activation in Schlemm's canal (SC) endothelium is required for the maintenance of IOP, making the angiopoietin/Tie2 pathway a target for new and potentially disease modifying g ... Full text Link to item Cite

Reduced Oxidative Phosphorylation and Increased Glycolysis in Human Glaucoma Lamina Cribrosa Cells.

Journal Article Invest Ophthalmol Vis Sci · November 2, 2020 PURPOSE: The lamina cribrosa (LC) is a key site of damage in glaucomatous optic neuropathy. We previously found that glaucoma LC cells have an increased profibrotic gene expression, with mitochondrial dysfunction in the form of decreased mitochondrial memb ... Full text Link to item Cite

miR-21-5p: A viable therapeutic strategy for regulating intraocular pressure.

Journal Article Exp Eye Res · November 2020 Lowering intraocular pressure (IOP) is the most effective treatment of glaucoma, however most of the current available glaucoma drugs target a single molecule. MicroRNAs (miRNAs) are noncoding RNAs that target a network of molecules. This study aims to inv ... Full text Link to item Cite

Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma.

Journal Article Small (Weinheim an der Bergstrasse, Germany) · October 2020 Increased stiffness of the Schlemm's canal (SC) endothelium in the aqueous humor outflow pathways has been associated with elevated intraocular pressure (IOP) in glaucoma. Novel treatments that relax this endothelium, such as actin depolymerizers and rho k ... Full text Cite

Physiologic Consequences of Caveolin-1 Ablation in Conventional Outflow Endothelia.

Journal Article Invest Ophthalmol Vis Sci · September 1, 2020 PURPOSE: Polymorphisms at the caveolin-1/2 locus are associated with glaucoma and IOP risk and deletion of caveolin-1 (Cav1) in mice elevates IOP and reduces outflow facility. However, the specific location/cell type responsible for Cav1-dependent regulati ... Full text Link to item Cite

Data on differentially expressed proteins in rock inhibitor-treated human trabecular meshwork cells using SWATH-based proteomics.

Journal Article Data Brief · August 2020 Rho-associated coiled coil-forming protein kinase (ROCK) inhibitors represent a novel class of anti-glaucoma drugs because of their ocular hypotensive effects. However, the underlying mechanisms responsible for lowering intraocular pressure (IOP) are not c ... Full text Link to item Cite

Integral role for lysyl oxidase-like-1 in conventional outflow tissue function and behavior.

Journal Article FASEB J · August 2020 Lysyl oxidase-like-1 (LOXL1), a vital crosslinking enzyme in elastin fiber maintenance, is essential for the stability and strength of elastic vessels and tissues. Variants in the LOXL1 locus associate with a dramatic increase in risk of exfoliation syndro ... Full text Link to item Cite

Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1.

Journal Article Hum Mol Genet · July 29, 2020 Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of ... Full text Link to item Cite

Fasudil Loaded PLGA Microspheres as Potential Intravitreal Depot Formulation for Glaucoma Therapy.

Journal Article Pharmaceutics · July 27, 2020 Rho-associated protein kinase (ROCK) inhibitors allow for causative glaucoma therapy. Unfortunately, topically applied ROCK inhibitors suffer from high incidence of hyperemia and low intraocular bioavailability. Therefore, we propose the use of poly (lacti ... Full text Link to item Cite

Molecular taxonomy of human ocular outflow tissues defined by single-cell transcriptomics.

Journal Article Proc Natl Acad Sci U S A · June 9, 2020 The conventional outflow pathway is a complex tissue responsible for maintaining intraocular pressure (IOP) homeostasis. The coordinated effort of multiple cells with differing responsibilities ensures healthy outflow function and IOP maintenance. Dysfunct ... Full text Link to item Cite

An In Vitro Bovine Cellular Model for Human Schlemm's Canal Endothelial Cells and Their Response to TGFβ Treatment.

Journal Article Transl Vis Sci Technol · June 2020 PURPOSE: Due to the limited availability of primary human Schlemm's canal (SC) endothelial cells, we aimed to develop an in vitro cellular model using the angular aqueous plexus (AAP) cells from bovine eyes. METHODS: We harvested a mixture of cells from th ... Full text Open Access Link to item Cite

Expression of mRNAs, miRNAs, and lncRNAs in Human Trabecular Meshwork Cells Upon Mechanical Stretch.

Journal Article Invest Ophthalmol Vis Sci · May 11, 2020 PURPOSE: Intraocular pressure (IOP), the primary risk factor for primary open-angle glaucoma, is determined by resistance to aqueous outflow through the trabecular meshwork (TM). IOP homeostasis relies on TM responses to mechanical stretch. To model the ef ... Full text Link to item Cite

Matrix Metalloproteinases and Glaucoma Treatment.

Journal Article J Ocul Pharmacol Ther · May 2020 Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade extracellular matrix (ECM) components such as collagen and have important roles in multiple biological processes, including development and tissue remodeling, both in health ... Full text Link to item Cite

Optogenetic stimulation of phosphoinositides reveals a critical role of primary cilia in eye pressure regulation.

Journal Article Sci Adv · May 2020 Glaucoma is a group of progressive optic neuropathies that cause irreversible vision loss. Although elevated intraocular pressure (IOP) is associated with the development and progression of glaucoma, the mechanisms for its regulation are not well understoo ... Full text Link to item Cite

Shear Stress in Schlemm's Canal as a Sensor of Intraocular Pressure.

Journal Article Sci Rep · April 2, 2020 Elevated intraocular pressure (IOP) narrows Schlemm's canal (SC), theoretically increasing luminal shear stress. Using engineered adenoviruses containing a functional fragment of the shear-responsive endothelial nitric oxide synthase (eNOS) promoter, we te ... Full text Link to item Cite

The β4-Subunit of the Large-Conductance Potassium Ion Channel KCa1.1 Regulates Outflow Facility in Mice.

Journal Article Invest Ophthalmol Vis Sci · March 9, 2020 PURPOSE: The large-conductance calcium-activated potassium channel KCa1.1 (BKCa, maxi-K) influences aqueous humor outflow facility, but the contribution of auxiliary β-subunits to KCa1.1 activity in the outflow pathway is unknown. METHODS: Using quantitati ... Full text Link to item Cite

R. Rand Allingham, M.D. (1953-2018).

Journal Article Exp Eye Res · March 2020 Full text Link to item Cite

Differential DNA methylation patterns in human Schlemm's canal endothelial cells with glaucoma.

Journal Article Mol Vis · 2020 PURPOSE: Schlemm's canal (SC) endothelial cells derived from donors with or without glaucoma showed different mechanical properties and gene expression. As an important contributor to the regulation of intraocular pressure (IOP) and pathogenesis of primary ... Link to item Cite

Increased stiffness and flow resistance of the inner wall of Schlemm's canal in glaucomatous human eyes.

Journal Article Proc Natl Acad Sci U S A · December 26, 2019 The cause of the elevated outflow resistance and consequent ocular hypertension characteristic of glaucoma is unknown. To investigate possible causes for this flow resistance, we used atomic force microscopy (AFM) with 10-µm spherical tips to probe the sti ... Full text Link to item Cite

Antiglaucoma EP2 Agonists: A Long Road That Led Somewhere.

Journal Article J Ocul Pharmacol Ther · November 2019 For >2 decades, EP2 agonists have been the subject of antiglaucoma research and development by scientists in industry and academia around the world. The road has led to the recent approval of the first drug of this class. This article reviews the developme ... Full text Link to item Cite

ISOPT Clinical Special Issue.

Journal Article J Ocul Pharmacol Ther · October 2019 Full text Link to item Cite

ENDOTHELIAL CAVEOLIN-1 DEFICIENCY RESULTS IN ENLARGED DISTAL VESSELS

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2019 Link to item Cite

Elevated IOP increases Shear Stress in Schlemm's Canal

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2019 Link to item Cite

In vivo measurement of TM stiffness: proof-of-principle in mice

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2019 Link to item Cite

microRNA21 mimics reduce intraocular pressure by PTEN/Akt/eNOS pathway

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2019 Link to item Cite

Age-related changes in eye morphology and aqueous humor dynamics in DBA/2J mice using contrast-enhanced ocular MRI.

Journal Article Magn Reson Imaging · June 2019 PURPOSE: Here, we are testing the hypothesis that dynamic contrast enhanced MRI (DCE-MRI) is a useful approach for non-invasively evaluating age-related changes in aqueous humor outflow and its contribution to elevated intraocular pressure in the DBA/2J mo ... Full text Link to item Cite

A Highly Effective and Ultra-Long-Acting Anti-Glaucoma Drug, with a Novel Periorbital Delivery Method.

Journal Article J Ocul Pharmacol Ther · June 2019 Purpose: Two features define the future of glaucoma therapeutics: (1) greatly improved ocular hypotensive efficacy and (2) a delivery method that improves patient convenience and compliance. A highly efficacious and extraordinarily long-acting ocular hypot ... Full text Link to item Cite

GPR158 in the Visual System: Homeostatic Role in Regulation of Intraocular Pressure.

Journal Article J Ocul Pharmacol Ther · May 2019 Purpose: GPR158 is a newly characterized family C G-protein-coupled receptor, previously identified in functional screens linked with biological stress, including one for susceptibility to ocular hypertension/glaucoma induced by glucocorticoid stress hormo ... Full text Link to item Cite

Probe Sensitivity to Cortical versus Intracellular Cytoskeletal Network Stiffness.

Journal Article Biophys J · February 5, 2019 In development, wound healing, and pathology, cell biomechanical properties are increasingly recognized as being of central importance. To measure these properties, experimental probes of various types have been developed, but how each probe reflects the p ... Full text Link to item Cite

A model of the oscillatory mechanical forces in the conventional outflow pathway.

Journal Article J R Soc Interface · January 31, 2019 Intraocular pressure is regulated by mechanosensitive cells within the conventional outflow pathway, the primary route of aqueous humour drainage from the eye. However, the characteristics of the forces acting on those cells are poorly understood. We devel ... Full text Link to item Cite

In vivo measurement of trabecular meshwork stiffness in a corticosteroid-induced ocular hypertensive mouse model.

Journal Article Proc Natl Acad Sci U S A · January 29, 2019 Ocular corticosteroids are commonly used clinically. Unfortunately, their administration frequently leads to ocular hypertension, i.e., elevated intraocular pressure (IOP), which, in turn, can progress to a form of glaucoma known as steroid-induced glaucom ... Full text Link to item Cite

Isolation of Retinal Exosome Biomarkers from Blood by Targeted Immunocapture.

Journal Article Adv Exp Med Biol · 2019 The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier, provides nutrients, recycles visual pigment, and removes spent discs from the photoreceptors, among many other functions. Because of these critical roles in visual homeostasis, t ... Full text Link to item Cite

Intracameral Delivery of Layer-by-Layer Coated siRNA Nanoparticles for Glaucoma Therapy.

Journal Article Small · December 2018 Glaucoma is the second leading cause of blindness worldwide, often associated with elevated intraocular pressure. Connective tissue growth factor (CTGF) is a mediator of pathological effects in the trabecular meshwork (TM) and Schlemm's canal (SC). A novel ... Full text Link to item Cite

Author Correction: Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers.

Journal Article Sci Rep · November 20, 2018 A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. ... Full text Link to item Cite

Accessibility to and Quality of Human Eye Tissue for Research: A Cross-Sectional Survey of ARVO Members.

Journal Article Invest Ophthalmol Vis Sci · October 1, 2018 PURPOSE: To assess experiences of vision scientists concerning the availability, quality, and documentation of human eye tissue for research, and to elicit researcher feedback about the establishment of an online portal that pairs eye bank capabilities wit ... Full text Link to item Cite

Pharmacological regulation of outflow resistance distal to Schlemm's canal.

Journal Article Am J Physiol Cell Physiol · July 1, 2018 The trabecular meshwork (TM) and Schlemm's canal generate the majority of outflow resistance; however, the distal regions of the conventional outflow pathway account for 25-50% of total resistance. Sections of distal vessels are surrounded by α-smooth musc ... Full text Link to item Cite

INDUCIBLE MMP-3 EXPRESSION IN A STEROID-INDUCED MURINE MODEL OF GLAUCOMA

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

Pentablock Copolymer Dexamethasone Nanoformulations Induced Ocular Hypertension in Mice

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

Homeostatic Role for GPR158 in Modulating Intraocular Pressure (IOP)

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

Long Non-Coding RNAs in Keratoconus-affected Human Cornea

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

TGF beta Signaling in Human Schlemm's Canal Endothelial Cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

sGC Stimulators and Trabecular Meshwork Biology

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

Modulation of outflow facility by the ocular pulse

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

Trabecular meshwork stiffness and outflow resistance are related

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

DISTAL OUTFLOW RESISTANCE CAN BE REGULATED PHARMACOLOGICALLY

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

ROLE OF CAVEOLAE AS MECHANOSENSORS IN SCHLEMM'S CANAL

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · July 1, 2018 Link to item Cite

Consensus recommendations for trabecular meshwork cell isolation, characterization and culture.

Journal Article Exp Eye Res · June 2018 Cultured trabecular meshwork (TM) cells are a valuable model system to study the cellular mechanisms involved in the regulation of conventional outflow resistance and thus intraocular pressure; and their dysfunction resulting in ocular hypertension. In thi ... Full text Link to item Cite

Differential Expression of Coding and Long Noncoding RNAs in Keratoconus-Affected Corneas.

Journal Article Invest Ophthalmol Vis Sci · June 1, 2018 PURPOSE: Keratoconus (KC) is the most common corneal ectasia. We aimed to determine the differential expression of coding and long noncoding RNAs (lncRNAs) in human corneas affected with KC. METHODS: From the corneas of 10 KC patients and 8 non-KC healthy ... Full text Open Access Link to item Cite

The relationship between outflow resistance and trabecular meshwork stiffness in mice.

Journal Article Sci Rep · April 11, 2018 It has been suggested that common mechanisms may underlie the pathogenesis of primary open-angle glaucoma (POAG) and steroid-induced glaucoma (SIG). The biomechanical properties (stiffness) of the trabecular meshwork (TM) have been shown to differ between ... Full text Link to item Cite

Differentially expressed microRNAs in the aqueous humor of patients with exfoliation glaucoma or primary open-angle glaucoma.

Journal Article Hum Mol Genet · April 1, 2018 Both exfoliation glaucoma (XFG) and primary open-angle glaucoma (POAG) have been linked to decreased conventional outflow of aqueous humor (AH). To better understand the molecular changes in the AH content under such conditions, we analyzed the miRNA profi ... Full text Link to item Cite

lncRNAs, DNA Methylation, and the Pathobiology of Exfoliation Glaucoma.

Journal Article J Glaucoma · March 2018 Exfoliation glaucoma (XFG) is a clinically aggressive and genetically distinct form of glaucoma that results in neuronal death and irreversible blindness. Gene variants associate with many neurodegenerative diseases including XFG, Parkinson's disease (PD) ... Full text Link to item Cite

Characterizing differences between MSCs and TM cells: Toward autologous stem cell therapies for the glaucomatous trabecular meshwork.

Journal Article J Tissue Eng Regen Med · March 2018 Glaucoma, a leading cause of blindness, is characterized by an increase in intraocular pressure, which is largely determined by resistance to aqueous humour outflow through the trabecular meshwork (TM). In glaucoma, the cellularity of the TM is decreased, ... Full text Link to item Cite

Physical exosome:exosome interactions.

Journal Article J Cell Mol Med · March 2018 Exosomes are extracellular nanovesicles that mediate a number of cellular processes, including intracellular signalling. There are many published examples of exosome-exosome dimers; however, their relevance has not been explored. Here, we propose that cell ... Full text Link to item Cite

Trabodenoson, an Adenosine Mimetic With A1 Receptor Selectivity Lowers Intraocular Pressure by Increasing Conventional Outflow Facility in Mice.

Journal Article Invest Ophthalmol Vis Sci · January 1, 2018 PURPOSE: To evaluate the relationship between the IOP-lowering effect of trabodenoson and the associated structural and functional changes in the trabecular meshwork (TM). METHODS: Six independent cohorts of young and aged mice were exposed to three differ ... Full text Link to item Cite

Polarized Exosome Release from the Retinal Pigmented Epithelium.

Journal Article Adv Exp Med Biol · 2018 The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier and provides nutrients and recycling of visual pigment to the photoreceptors, among many other functions. The RPE is also a key site of pathophysiological changes in age-related m ... Full text Link to item Cite

A Review of Nitric Oxide for the Treatment of Glaucomatous Disease.

Journal Article Ophthalmol Ther · December 2017 Glaucoma is the leading cause of irreversible blindness worldwide, affecting 64.3 million people. An estimated 60.5 million people are affected by primary open angle glaucoma globally, and this will increase to 111.8 million by 2040. The definition of glau ... Full text Link to item Cite

New Insight of Common Regulatory Pathways in Human Trabecular Meshwork Cells in Response to Dexamethasone and Prednisolone Using an Integrated Quantitative Proteomics: SWATH and MRM-HR Mass Spectrometry.

Journal Article Journal of proteome research · October 2017 The molecular pathophysiology of corticosteroid-induced ocular hypertension (CIH) is not well understood. To determine the biological mechanisms of CIH, this study investigated protein expression profiles of human trabecular meshwork (hTM) cells in respons ... Full text Cite

The Ability of Nitric Oxide to Lower Intraocular Pressure Is Dependent on Guanylyl Cyclase.

Journal Article Investigative ophthalmology & visual science · September 2017 PurposeWhile nitric oxide (NO) donors are emerging as treatments for glaucoma, the mechanism by which NO lowers intraocular pressure (IOP) is unclear. NO activates the enzyme guanylyl cyclase (GC) to produce cyclic guanosine monophosphate. We stud ... Full text Cite

Peptide-Functionalized Fluorescent Particles for In Situ Detection of Nitric Oxide via Peroxynitrite-Mediated Nitration.

Journal Article Adv Healthc Mater · August 2017 Nitric oxide (NO) is a free radical signaling molecule that plays a crucial role in modulating physiological homeostasis across multiple biological systems. NO dysregulation is linked to the pathogenesis of multiple diseases; therefore, its quantification ... Full text Link to item Cite

Pentablock copolymer dexamethasone nanoformulations elevate MYOC: in vitro liberation, activity and safety in human trabecular meshwork cells.

Journal Article Nanomedicine (Lond) · August 2017 AIM: The aim of this study is to examine the elevation of MYOC in long-term treatment of human trabecular meshwork (HTM) cells using dexamethasone (DEX) encapsulated pentablock (PB) copolymer-based nanoparticles (NPs) (DEX-PB-NPs). MATERIALS & METHODS: PB ... Full text Link to item Cite

Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers.

Journal Article Sci Rep · July 7, 2017 The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier in the eye and its polarity is responsible for directional secretion and uptake of proteins, lipoprotein particles and extracellular vesicles (EVs). Such a secretional division di ... Full text Open Access Link to item Cite

Roles of exosomes in the normal and diseased eye.

Journal Article Prog Retin Eye Res · July 2017 Exosomes are nanometer-sized vesicles that are released by cells in a controlled fashion and mediate a plethora of extra- and intercellular activities. Some key functions of exosomes include cell-cell communication, immune modulation, extracellular matrix ... Full text Link to item Cite

Effects of dexamethasone on trabecular meshwork stiffness in mice

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2017 Link to item Cite

Stretch-Dependent Pore Formation in Glaucomatous Schlemm's Canal Cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2017 Link to item Cite

Performance of shear stress-responsive reporter viruses in human Schlemm's canal monolayers

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2017 Link to item Cite

Netarsudil increases size of giant vacuoles in Schlemm's canal of perfused human eyes

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2017 Link to item Cite

Nitric oxide changes the biomechanical behavior of Schlemm canal cells and HUVECs

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2017 Link to item Cite

The role of alpha-actinin and RhoA in the mechanical properties of Schlemm's canal cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2017 Link to item Cite

The many faces of the trabecular meshwork cell.

Journal Article Exp Eye Res · May 2017 With the combined purpose of facilitating useful vision over a lifetime, a number of ocular cells have evolved specialized features not found elsewhere in the body. The trabecular meshwork (TM) cell at the irido-corneal angle, which is a key regulator of i ... Full text Link to item Cite

Stanniocalcin-1 Is an Ocular Hypotensive Agent and a Downstream Effector Molecule That Is Necessary for the Intraocular Pressure-Lowering Effects of Latanoprost.

Journal Article Invest Ophthalmol Vis Sci · May 1, 2017 PURPOSE: To identify downstream signaling molecules through which intraocular pressure (IOP) is lowered following treatment with the prostaglandin analog latanoprost. METHODS: Total RNA and protein isolated from primary human Schlemm's canal cells (n = 3) ... Full text Link to item Cite

Introduction to Gedenkschrift for David L. Epstein, MD

Journal Article EXPERIMENTAL EYE RESEARCH · May 1, 2017 Full text Link to item Cite

Localized and Controlled Delivery of Nitric Oxide to the Conventional Outflow Pathway via Enzyme Biocatalysis: Toward Therapy for Glaucoma.

Journal Article Adv Mater · April 2017 Nitric oxide (NO) is able to lower intraocular pressure (IOP); however, its therapeutic effects on outflow physiology are location- and dose-dependent. A NO delivery platform that directly targets the resistance-generating region of the conventional outflo ... Full text Link to item Cite

Therapeutic potential of AAV-mediated MMP-3 secretion from corneal endothelium in treating glaucoma.

Journal Article Hum Mol Genet · April 1, 2017 Intraocular pressure (IOP) is maintained as a result of the balance between production of aqueous humour (AH) by the ciliary processes and hydrodynamic resistance to its outflow through the conventional outflow pathway comprising the trabecular meshwork (T ... Full text Link to item Cite

VEGF as a Paracrine Regulator of Conventional Outflow Facility.

Journal Article Invest Ophthalmol Vis Sci · March 1, 2017 PURPOSE: Vascular endothelial growth factor (VEGF) regulates microvascular endothelial permeability, and the permeability of Schlemm's canal (SC) endothelium influences conventional aqueous humor outflow. We hypothesize that VEGF signaling regulates outflo ... Full text Link to item Cite

Intravitreal Anti-VEGF Injections Reduce Aqueous Outflow Facility in Patients With Neovascular Age-Related Macular Degeneration.

Journal Article Invest Ophthalmol Vis Sci · March 1, 2017 PURPOSE: We assess the effect of intravitreal anti-VEGF injections on tonographic outflow facility. METHODS: Patients with age-related macular degeneration who had received unilateral intravitreal anti-VEGF injections were recruited into two groups, those ... Full text Link to item Cite

Differential response and withdrawal profile of glucocorticoid-treated human trabecular meshwork cells.

Journal Article Exp Eye Res · February 2017 The goal of the study was to examine secreted protein response and withdrawal profiles from cultured human trabecular meshwork (HTM) cells following short- and long-term glucocorticoid treatment. Primary cultures of five human HTM cell strains isolated fro ... Full text Link to item Cite

Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia.

Journal Article Sci Rep · January 16, 2017 The juxtacanalicular connective tissue of the trabecular meshwork together with inner wall endothelium of Schlemm's canal (SC) provide the bulk of resistance to aqueous outflow from the anterior chamber. Endothelial cells lining SC elaborate tight junction ... Full text Link to item Cite

Major review: Exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology.

Journal Article Exp Eye Res · January 2017 Exfoliation syndrome (XFS) is a common age-related disorder that leads to deposition of extracellular fibrillar material throughout the body. The most recognized disease manifestation is exfoliation glaucoma (XFG), which is a common cause of blindness worl ... Full text Link to item Cite

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine.

Journal Article Prog Retin Eye Res · January 2017 Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expres ... Full text Link to item Cite

A Comparative Study of Serum Exosome Isolation Using Differential Ultracentrifugation and Three Commercial Reagents.

Journal Article PLoS One · 2017 Exosomes play a role in cell-to-cell signaling and serve as possible biomarkers. Isolating exosomes with reliable quality and substantial concentration is a major challenge. Our purpose is to compare the exosomes extracted by three different exosome isolat ... Full text Link to item Cite

Regulatory Roles of Anoctamin-6 in Human Trabecular Meshwork Cells.

Journal Article Invest Ophthalmol Vis Sci · January 1, 2017 PURPOSE: Trabecular meshwork (TM) cell volume is a determinant of aqueous humor outflow resistance, and thereby IOP. Regulation of TM cell volume depends on chloride ion (Cl-) release through swelling-activated channels (ICl,Swell), whose pore is formed by ... Full text Link to item Cite

Prdx6 retards senescence and restores trabecular meshwork cell health by regulating reactive oxygen species.

Journal Article Cell Death Discov · 2017 A progressive decline in antioxidant potential and accumulation of reactive oxygen species (ROS) are major causes of pathogenesis of several diseases, including glaucoma. Trabecular meshwork (TM) dysfunction resulting in higher intraocular pressure (IOP) i ... Full text Link to item Cite

Caveolin-1 modulates intraocular pressure: implications for caveolae mechanoprotection in glaucoma.

Journal Article Sci Rep · November 14, 2016 Polymorphisms in the CAV1/2 genes that encode signature proteins of caveolae are associated with glaucoma, the second leading cause of blindness worldwide, and with its major risk factor, intraocular pressure (IOP). We hypothesized that caveolin-1 (Cav-1) ... Full text Link to item Cite

Netarsudil Increases Outflow Facility in Human Eyes Through Multiple Mechanisms.

Journal Article Invest Ophthalmol Vis Sci · November 1, 2016 PURPOSE: Netarsudil is a Rho kinase/norepinephrine transporter inhibitor currently in phase 3 clinical development for glaucoma treatment. We investigated the effects of its active metabolite, netarsudil-M1, on outflow facility (C), outflow hydrodynamics, ... Full text Link to item Cite

Life under pressure: The role of ocular cribriform cells in preventing glaucoma.

Journal Article Exp Eye Res · October 2016 Primary open-angle glaucoma is a multifactorial blinding disease often impacting the two pressure-sensitive regions of the eye: the conventional outflow pathway and the optic nerve head (ONH). The connective tissues that span these two openings in the glob ... Full text Link to item Cite

The Value of Mouse Models for Glaucoma Drug Discovery.

Journal Article J Ocul Pharmacol Ther · October 2016 Full text Link to item Cite

Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes.

Journal Article Eur J Pharmacol · September 15, 2016 Visual impairment due to glaucoma currently impacts 70 million people worldwide. While disease progression can be slowed or stopped with effective lowering of intraocular pressure, current medical treatments are often inadequate. Fortunately, three new cla ... Full text Link to item Cite

IOP-induced Changes in Schlemm's Canal Dimensions and the Relation to Shear Stress

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

Segmentation and analysis software for mapping aqueous humor outflow pattern in living mice

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

Real-time Visualization of AR-13324 Effects on Schlemm's Canal and Scleral Vessels in Living Mice

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

Functional renin receptors in human Schlemm's Canal cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

Role of microRNAs in glaucomatous outflow resistance dysregulation

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

The Soluble Guanylate Cyclase Stimulator IWP-953 Increases Conventional Outflow Facility in Mouse Eyes

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

The mechanisms of increasing outflow facility by AR-13324M in human eyes

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

A role for exosomes in steroid induced ECM accumulation in the TM

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · September 1, 2016 Link to item Cite

A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium.

Journal Article Invest Ophthalmol Vis Sci · August 1, 2016 PURPOSE: Noncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG). METHODS: Using the NEIGHBORHOOD data set (3853 ... Full text Link to item Cite

Eye Care Professionals' Perspectives on Eye Donation and an Eye Donation Registry for Research: A Single-Institution, Cross-Sectional Study.

Journal Article Curr Eye Res · June 2016 PURPOSE: A centralized eye donation registry for research could help to bridge the gap between patients interested in donating their eyes to science and scientists who conduct research on human eye tissue. Previous research has demonstrated patient and fam ... Full text Link to item Cite

Successful Implementation of a Program for Increasing Donor Eyes for Research: The Duke-Miracles In Sight Program.

Journal Article J Ocul Pharmacol Ther · April 2016 PURPOSE: Although essential for development of ocular therapeutics, the quality and quantity of human donor eyes for research have been on the decline. To streamline procurement protocols, provide better medical documentation of tissue, and improve freshne ... Full text Link to item Cite

The Soluble Guanylate Cyclase Stimulator IWP-953 Increases Conventional Outflow Facility in Mouse Eyes.

Journal Article Invest Ophthalmol Vis Sci · March 2016 PURPOSE: The nitric oxide (NO)-cyclic guanosine-3',5'-monophosphate (cGMP) pathway regulates aqueous humor outflow and therefore, intraocular pressure. We investigated the pharmacologic effects of the soluble guanylate cyclase (sGC) stimulator IWP-953 on p ... Full text Link to item Cite

Mechanism of Fibronectin Binding to Human Trabecular Meshwork Exosomes and Its Modulation by Dexamethasone.

Journal Article PLoS One · 2016 Exosomes are emerging as important mediators of cell-matrix interactions by means of specific adhesion proteins. Changes in the tissue-specific exosomal protein expression may underlie pathological conditions whereby extracellular matrix turnover and homeo ... Full text Link to item Cite

Role of anoctamin in glaucoma and cancer

Conference INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE · January 1, 2016 Link to item Cite

Physical Factors Affecting Outflow Facility Measurements in Mice.

Journal Article Invest Ophthalmol Vis Sci · December 2015 PURPOSE: Mice are commonly used to study conventional outflow physiology. This study examined how physical factors (hydration, temperature, and anterior chamber [AC] deepening) influence ocular perfusion measurements in mice. METHODS: Outflow facility (C) ... Full text Link to item Cite

Genetic variants and cellular stressors associated with exfoliation syndrome modulate promoter activity of a lncRNA within the LOXL1 locus.

Journal Article Hum Mol Genet · November 15, 2015 Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly ... Full text Link to item Cite

A biomimetic Schlemm's canal inner wall: A model to study outflow physiology, glaucoma pathology and high-throughput drug screening.

Journal Article Biomaterials · October 2015 Glaucoma is a disease that damages the optic nerve, frequently leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, which is expected to affect 80 million people by 2020, causing bilateral blindness in ... Full text Link to item Cite

Expression Profiling of Human Schlemm's Canal Endothelial Cells From Eyes With and Without Glaucoma.

Journal Article Invest Ophthalmol Vis Sci · October 2015 PURPOSE: Ocular hypertension is a major risk factor for glaucoma and the inner wall of Schlemm's canal (SC) endothelia participates in the regulation of aqueous humor outflow resistance. This study aimed to identify differentially expressed genes in primar ... Full text Link to item Cite

High-throughput screening for modulators of cellular contractile force.

Journal Article Integr Biol (Camb) · October 2015 When cellular contractile forces are central to pathophysiology, these forces comprise a logical target of therapy. Nevertheless, existing high-throughput screens are limited to upstream signalling intermediates with poorly defined relationships to such a ... Full text Link to item Cite

Role of nitric oxide in murine conventional outflow physiology.

Journal Article Am J Physiol Cell Physiol · August 15, 2015 Elevated intraocular pressure (IOP) is the main risk factor for glaucoma. Exogenous nitric oxide (NO) decreases IOP by increasing outflow facility, but whether endogenous NO production contributes to the physiological regulation of outflow facility is uncl ... Full text Link to item Cite

Recreation of a 3-D Physiological Model of Conventional Outflow Tract in vitro

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2015 Link to item Cite

Baicalein lowers intraocular pressure and increases outflow facility in mouse eye

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2015 Link to item Cite

Trabecular Meshwork Exosomes: Fibronectin Binding and ECM homeostasis

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2015 Link to item Cite

The Effects of VEGF and anti-VEGF on Outflow Facility in Mice and Humans

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2015 Link to item Cite

Aqueous humor outflow: dynamics and disease.

Journal Article Invest Ophthalmol Vis Sci · May 2015 Full text Link to item Cite

The "T" in JOPT.

Other J Ocul Pharmacol Ther · April 2015 Full text Link to item Cite

Autophagic dysregulation in glaucomatous trabecular meshwork cells.

Journal Article Biochim Biophys Acta · March 2015 Primary open angle glaucoma (POAG) is a degenerative disease commonly associated with aging and elevated intraocular pressure (IOP). Higher resistance to aqueous humor (AH) outflow through the trabecular meshwork (TM) generates the elevated IOP in POAG; un ... Full text Link to item Cite

Human aqueous humor exosomes.

Journal Article Exp Eye Res · March 2015 Aqueous humor (AH) is a dynamic intraocular fluid that supports the vitality of tissues that regulate intraocular pressure. We recently discovered that extracellular nanovesicles called exosomes are a major constituent of AH. Exosomes function in extracell ... Full text Link to item Cite

Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction.

Journal Article Prog Retin Eye Res · January 2015 Ocular hypertension in glaucoma develops due to age-related cellular dysfunction in the conventional outflow tract, resulting in increased resistance to aqueous humor outflow. Two cell types, trabecular meshwork (TM) and Schlemm's canal (SC) endothelia, in ... Full text Link to item Cite

Controlled exosome release from the retinal pigment epithelium in situ.

Journal Article Exp Eye Res · December 2014 Retinal Pigment Epithelial cells (RPE) express both GPR143 and myocilin, which interact in a signal transduction-dependent manner. In heterologous systems, activation of GPR143 with ligand causes transient recruitment of myocilin to internalized receptors, ... Full text Link to item Cite

Shear stress-triggered nitric oxide release from Schlemm's canal cells.

Journal Article Invest Ophthalmol Vis Sci · November 13, 2014 PURPOSE: Endothelial nitric oxide (NO) synthase is regulated by shear stress. At elevated intraocular pressures when the Schlemm's canal (SC) begins to collapse, shear stress is comparable with that in large arteries. We investigated the relationship betwe ... Full text Link to item Cite

Endothelial nitric oxide synthase-related mechanotransduction changes in aged porcine angular aqueous plexus cells.

Journal Article Invest Ophthalmol Vis Sci · November 6, 2014 PURPOSE: To investigate effects of aging on endothelial nitric oxide synthase (eNOS) expression and signaling in angular aqueous plexus (AAP) (functional equivalent to human Schlemm's canal) cells subjected to shear stress. METHODS: The AAP cells were isol ... Full text Link to item Cite

Biomechanical strain as a trigger for pore formation in Schlemm's canal endothelial cells.

Journal Article Exp Eye Res · October 2014 The bulk of aqueous humor passing through the conventional outflow pathway must cross the inner wall endothelium of Schlemm's canal (SC), likely through micron-sized transendothelial pores. SC pore density is reduced in glaucoma, possibly contributing to o ... Full text Link to item Cite

Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma.

Journal Article Proc Natl Acad Sci U S A · September 23, 2014 Increased flow resistance is responsible for the elevated intraocular pressure characteristic of glaucoma, but the cause of this resistance increase is not known. We tested the hypothesis that altered biomechanical behavior of Schlemm's canal (SC) cells co ... Full text Link to item Cite

Ultrastructural changes associated with dexamethasone-induced ocular hypertension in mice.

Journal Article Invest Ophthalmol Vis Sci · July 15, 2014 PURPOSE: To determine whether dexamethasone (DEX)-induced ocular hypertension (OHT) in mice mimics the hallmarks of steroid-induced glaucoma (SIG) in humans, including reduced conventional outflow facility (C), increased extracellular matrix (ECM), and myo ... Full text Link to item Cite

The structure of the trabecular meshwork, its connections to the ciliary muscle, and the effect of pilocarpine on outflow facility in mice.

Journal Article Invest Ophthalmol Vis Sci · May 15, 2014 PURPOSE: To determine the connections between the ciliary muscle (CM), trabecular meshwork (TM), and Schlemm's canal (SC) and their innervations that allows CM contraction (by pilocarpine) to influence conventional outflow in mice. METHODS: Sequential sect ... Full text Link to item Cite

Cell senescence reduced the mechanotransduction sensitivity of porcine angular aqueous plexus cells to elevation of pressure.

Journal Article Invest Ophthalmol Vis Sci · April 11, 2014 PURPOSE: To investigate the effect of pressure/flow on the barrier function and protein expression of normal and senescent porcine aqueous humor plexus (AAP) cells, which are the porcine equivalent of human Schlemm's canal endothelial cells. METHODS: AAP c ... Full text Link to item Cite

Dynamic alterations in conventional outflow function in Bmp2-induced ocular hypertensive mice

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

Role of VEGF in Conventional Outflow Homeostasis

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

A fluorescent permeability assay for Schlemm's canal endothelial cells in response to stretch

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

Myocilin Mutations Alter GPCR Endocytosis

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

Myocilin is constitutively released with exosomes from RPE in situ

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

Differential effects of nitric oxide synthase inhibitors on conventional outflow facility in mice

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

Trabecular meshwork exosomes enhance cellular collagen uptake

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

Role of Caveolin-1 in Intraocular Pressure and Conventional Outflow Regulation

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

Mechanosensitivity of Schlemm's canal endothelial cells from normal and glaucomatous eyes

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

The Effect of Cell Stiffness on I- and B-Pore Formation in Schlemm's Canal Endothelial Cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · April 1, 2014 Link to item Cite

Pilocarpine-induced dilation of Schlemm's canal and prevention of lumen collapse at elevated intraocular pressures in living mice visualized by OCT.

Journal Article Invest Ophthalmol Vis Sci · March 4, 2014 PURPOSE: The goal was to assess effects of IOP and pilocarpine-induced ciliary muscle contraction on conventional outflow pathway tissues in living anesthetized mice. METHODS: Intraocular pressure was controlled by intracameral cannulation of mouse eyes wh ... Full text Link to item Cite

Concentration-related effects of nitric oxide and endothelin-1 on human trabecular meshwork cell contractility.

Journal Article Exp Eye Res · March 2014 The contractility status of trabecular meshwork (TM) cells influences aqueous humor outflow resistance and intraocular pressure. Using human TM cells as a model, the goal of the present study was to examine concentration-response relationships of two proto ... Full text Link to item Cite

Circumferential tensile stiffness of glaucomatous trabecular meshwork.

Journal Article Invest Ophthalmol Vis Sci · February 10, 2014 PURPOSE: Our previous work indicated that a larger circumferential Young's modulus (E) of trabecular meshwork (TM) correlated with a higher outflow facility (C) in normal human donor eyes. The current study investigated the influence of glaucomatous TM sti ... Full text Link to item Cite

Thirty years of JOPT.

Other J Ocul Pharmacol Ther · February 2014 Full text Link to item Cite

Disease progression in iridocorneal angle tissues of BMP2-induced ocular hypertensive mice with optical coherence tomography.

Journal Article Mol Vis · 2014 PURPOSE: The goal of the present study was to test for the first time whether glaucomatous-like disease progression in a mouse can be assessed morphologically and functionally with spectral domain optical coherence tomography (SD-OCT). METHODS: We monitore ... Link to item Cite

Pigment epithelium-derived factor decreases outflow facility.

Journal Article Invest Ophthalmol Vis Sci · October 11, 2013 PURPOSE: Pigment epithelium-derived factor (PEDF) regulates blood-retinal barrier function. As a constituent of aqueous humor, the role of PEDF in conventional outflow function is unknown. The goals of the study were to examine the effects of PEDF on barri ... Full text Link to item Cite

Gene expression profile in human trabecular meshwork from patients with primary open-angle glaucoma.

Journal Article Invest Ophthalmol Vis Sci · September 27, 2013 PURPOSE: To identify the specific genes in human trabecular meshwork (TM) related to POAG. METHODS: Primary open-angle glaucoma TM specimens were obtained from routine trabeculectomy surgery. Nonglaucomatous control TM specimens were dissected from donor e ... Full text Link to item Cite

Oxidative stress impact on barrier function of porcine angular aqueous plexus cell monolayers.

Journal Article Invest Ophthalmol Vis Sci · July 18, 2013 PURPOSE: Our goal was to investigate the effect of chronic oxidative stress on angular aqueous plexus (AAP, functional equivalent to human Schlemm's canal) endothelial cells from porcine eyes. METHODS: AAP cells were differentially isolated from porcine ou ... Full text Link to item Cite

Differential effects of prostaglandin E2-sensitive receptors on contractility of human ocular cells that regulate conventional outflow.

Journal Article Invest Ophthalmol Vis Sci · July 16, 2013 PURPOSE: The goal of this study was to functionally compare prostaglandin E2 (PGE2)-sensitive receptors in human primary cells involved in conventional outflow. METHODS: The expression profile of prostaglandin (PG) receptors in primary cultures of human tr ... Full text Link to item Cite

PEDF Effects on Outflow Facility

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

Circumferential Trabecular Meshwork Stiffness in Glaucomatous Eyes

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

Shear Stress Stimulation of NO release from Schlemm's Canal Cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

DIMINISHED AUTOPHAGIC CAPACITY OF GLAUCOMATOUS TRABECULAR MESHWORK CELLS

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

Effects of Nitric Oxide Donor on Outflow Facility in Mice

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

Metabolic Dependence of Conventional Outflow Facility in Mice

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

Regulatory Roles of Anoctamin-6 in Human Trabecular Meshwork Cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

Monolayer traction forces of Schlemm's canal endothelial cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

Oxidative Stress Impacts On Barrier Function of Porcine Angular Aqueous Plexus Cell Monolayers

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

A Role for Myocilin in Receptor Endocytosis

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

Sphingosine-1-Phosphate signaling in cultured human trabecular meshwork cells

Conference INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE · June 1, 2013 Link to item Cite

Optimizing gene transfer to conventional outflow cells in living mouse eyes.

Journal Article Exp Eye Res · April 2013 The mouse eye has physiological and genetic advantages to study conventional outflow function. However, its small size and shallow anterior chamber presents technical challenges to efficient intracameral delivery of genetic material to conventional outflow ... Full text Link to item Cite

Unique response profile of trabecular meshwork cells to the novel selective glucocorticoid receptor agonist, GW870086X.

Journal Article Invest Ophthalmol Vis Sci · March 1, 2013 PURPOSE: Glucocorticoid (GC)-induced glaucoma is an undesirable side effect of traditional GCs. Ocular hypertension responsible for GC-induced glaucoma is due to alterations in conventional outflow homeostasis. The present study evaluates a novel selective ... Full text Link to item Cite

The effect of Rho-associated kinase inhibition on the ocular penetration of timolol maleate.

Journal Article Invest Ophthalmol Vis Sci · February 7, 2013 PURPOSE: To assess the effects of Rho-associated kinase (ROCK) inhibition on the intraocular penetration of timolol maleate. METHODS: Ex vivo porcine corneal penetration of timolol maleate, sotalol hydrochloride, or brinzolamide incubated with or without Y ... Full text Link to item Cite

sCD44 overexpression increases intraocular pressure and aqueous outflow resistance.

Journal Article Mol Vis · 2013 PURPOSE: CD44 plays major roles in multiple physiologic processes. The ectodomain concentration of the CD44 receptor, soluble CD44 (sCD44), is significantly increased in the aqueous humor of primary open-angle glaucoma (POAG). The purpose of this study was ... Link to item Cite

A role for myocilin in receptor-mediated endocytosis.

Journal Article PLoS One · 2013 Myocilin is a broadly expressed protein that when mutated uniquely causes glaucoma. While no function has been ascribed to explain focal disease, some properties of myocilin are known. Myocilin is a cytoplasmic protein that also localizes to vesicles speci ... Full text Link to item Cite

Pore formation in Schlemm's canal endothelial cells is mechano-sensitive and impaired in glaucoma

Conference ASME 2012 Summer Bioengineering Conference, SBC 2012 · December 1, 2012 Increased intraocular pressure (IOP) is the leading risk factor for glaucoma, but the mechanisms of IOP regulation during normalcy and disease are poorly understood. Considerable evidence suggests that Schlemm's canal (SC) endothelial cells may influence I ... Full text Cite

New developments for JOPT

Other Journal of Ocular Pharmacology and Therapeutics · October 1, 2012 Full text Cite

Pharmacologic manipulation of conventional outflow facility in ex vivo mouse eyes.

Journal Article Invest Ophthalmol Vis Sci · August 24, 2012 PURPOSE: Mouse models are useful for glaucoma research, but it is unclear whether intraocular pressure (IOP) regulation in mice operates through mechanisms similar to those in humans. Our goal was to determine whether pharmacologic compounds that affect co ... Full text Link to item Cite

Differential effects of trabecular meshwork stiffness on outflow facility in normal human and porcine eyes.

Journal Article Invest Ophthalmol Vis Sci · August 9, 2012 PURPOSE: The study was designed to determine trabecular meshwork (TM) stiffness and its relationship to outflow facility (C) in perfused normal human and porcine eyes. METHODS: Human and porcine eyes were perfused at pressures of 10, 20, 30, and 40 mm Hg t ... Full text Link to item Cite

Mechanical responsiveness of the endothelial cell of Schlemm's canal: scope, variability and its potential role in controlling aqueous humour outflow.

Journal Article J R Soc Interface · June 7, 2012 Primary open-angle glaucoma is associated with elevated intraocular pressure, which in turn is believed to result from impaired outflow of aqueous humour. Aqueous humour outflow passes mainly through the trabecular meshwork (TM) and then through pores form ... Full text Link to item Cite

Myocilin, a component of a membrane-associated protein complex driven by a homologous Q-SNARE domain.

Journal Article Biochemistry · May 1, 2012 Myocilin is a widely expressed protein with no known function; however, mutations in myocilin appear to manifest uniquely as ocular hypertension and the blinding disease of glaucoma. Using the protein homology/analogy recognition engine (Phyre), we find th ... Full text Link to item Cite

Stimulation of aquaporin-mediated fluid transport by cyclic GMP in human retinal pigment epithelium in vitro.

Journal Article Invest Ophthalmol Vis Sci · April 24, 2012 PURPOSE: The retinal pigment epithelium (RPE) expresses aquaporin-1 (AQP1) and components of the natriuretic peptide signaling pathway. We hypothesized that stimulation of the natriuretic signaling pathway in RPE with atrial natriuretic peptide (ANP) and w ... Full text Link to item Cite

Moving forward in ocular pharmacology.

Other J Ocul Pharmacol Ther · April 2012 Full text Link to item Cite

Protein markers and differentiation in culture for Schlemm's canal endothelial cells.

Journal Article Exp Eye Res · March 2012 The two cell types that populate the human conventional outflow pathway, Schlemm's canal (SC) and trabecular meshwork (TM) regulate intraocular pressure. In culture, SC and TM cells have been useful tools toward understanding their respective roles in conv ... Full text Link to item Cite

Effects of cardiotonic steroids on trabecular meshwork cells: search for mediator of ouabain-enhanced outflow facility.

Journal Article Exp Eye Res · March 2012 Lowering intraocular pressure (IOP) is currently the only strategy documented to slow the onset and progression of glaucomatous blindness. Ouabain, a cardiotonic glycoside inhibitor of Na(+), K(+)-activated ATPase, was recently reported to enhance outflow ... Full text Link to item Cite

Current understanding of conventional outflow dysfunction in glaucoma.

Journal Article Curr Opin Ophthalmol · March 2012 PURPOSE OF REVIEW: Regulation of intraocular pressure by the conventional (trabecular) outflow pathway is complicated, involving a myriad of mechanical and chemical signals. In most, intraocular pressure is maintained within a tight range over a lifetime. ... Full text Link to item Cite

Mechanisms of ATP release by human trabecular meshwork cells, the enabling step in purinergic regulation of aqueous humor outflow.

Journal Article J Cell Physiol · January 2012 Our guiding hypothesis is that ecto-enzymatic conversion of extracellular ATP to adenosine activates A(1) adenosine receptors, reducing resistance to aqueous humor outflow and intraocular pressure. The initial step in this purinergic regulation is ATP rele ... Full text Link to item Cite

eNOS, a pressure-dependent regulator of intraocular pressure.

Journal Article Invest Ophthalmol Vis Sci · December 9, 2011 PURPOSE: Pathology in the primary drainage pathway for aqueous humor in the eye is responsible for ocular hypertension, the only treatable risk factor in patients with glaucoma. Unfortunately, the mechanisms that regulate pressure-dependent drainage of aqu ... Full text Link to item Cite

Cytoskeletal dependence of adenosine triphosphate release by human trabecular meshwork cells.

Journal Article Invest Ophthalmol Vis Sci · October 10, 2011 PURPOSE: To test whether adenosine triphosphate (ATP) release links cytoskeletal remodeling with release of matrix metalloproteinases (MMPs), regulators of outflow facility and intraocular pressure. METHODS: ATP release was measured by luciferin-luciferase ... Full text Link to item Cite

The role of the prostaglandin EP4 receptor in the regulation of human outflow facility.

Journal Article Invest Ophthalmol Vis Sci · June 1, 2011 PURPOSE: Activation of prostaglandin (PG)-EP(4) receptors by 3,7-dithiaPGE(1) robustly lowers intraocular pressure in nonhuman primate eyes, which increases outflow facility but has no effect on aqueous secretion or uveoscleral outflow. Because of differen ... Full text Link to item Cite

Protein profile of exosomes from trabecular meshwork cells.

Journal Article J Proteomics · May 16, 2011 To better understand the role of exosomes in the trabecular meshwork (TM), the site of intraocular pressure control, the exosome proteome from primary cultures of human TM cell monolayers was analyzed. Exosomes were purified from urine and conditioned medi ... Full text Link to item Cite

S1P₂ receptor regulation of sphingosine-1-phosphate effects on conventional outflow physiology.

Journal Article Am J Physiol Cell Physiol · May 2011 Elevated intraocular pressure is the main risk factor in primary open-angle glaucoma, involving an increased resistance to aqueous humor outflow in the juxtacanalicular region of the conventional outflow pathway which includes the trabecular meshwork (TM) ... Full text Link to item Cite

Outflow physiology of the mouse eye: pressure dependence and washout.

Journal Article Invest Ophthalmol Vis Sci · March 2011 PURPOSE: Mice are commonly used in glaucoma research, but relatively little is known about aqueous outflow dynamics in the species. To facilitate future use of the mouse as a model of aqueous humor outflow, several fundamental physiological parameters were ... Full text Link to item Cite

Structural basement membrane components and corresponding integrins in Schlemm's canal endothelia.

Journal Article Mol Vis · January 19, 2011 PURPOSE: The conventional outflow pathway provides the primary source of resistance to aqueous humor drainage, regulating intraocular pressure. Despite large pressure gradients across the inner wall of Schlemm's canal (SC), cells remain attached to their b ... Link to item Cite

Mechanisms of ATP release, the enabling step in purinergic dynamics.

Journal Article Cell Physiol Biochem · 2011 The only effective intervention to slow onset and progression of glaucomatous blindness is to lower intraocular pressure (IOP). Among other modulators, adenosine receptors (ARs) exert complex regulation of IOP. Agonists of A(3)ARs in the ciliary epithelium ... Full text Link to item Cite

A model of giant vacuole dynamics in human Schlemm's canal endothelial cells.

Journal Article Exp Eye Res · January 2011 Aqueous humour transport across the inner wall endothelium of Schlemm's canal likely involves flow through giant vacuoles and pores, but the mechanics of how these structures form and how they influence the regulation of intraocular pressure (IOP) are not ... Full text Link to item Cite

Sphingosine-1-phosphate enhancement of cortical actomyosin organization in cultured human Schlemm's canal endothelial cell monolayers.

Journal Article Invest Ophthalmol Vis Sci · December 2010 PURPOSE: Perfusion of sphingosine-1-phosphate (S1P) in whole eye organ culture models decreases outflow facility, whereas S1P promotes stress fiber formation and contractility in cultured trabecular meshwork (TM) cells. Because of S1P's known effect of inc ... Full text Link to item Cite

Myocilin levels in primary open-angle glaucoma and pseudoexfoliation glaucoma human aqueous humor.

Journal Article J Glaucoma · December 2010 PURPOSE: To determine the concentration of myocilin in primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG) aqueous humor. METHODS: Aqueous humor was collected during surgery from patients with POAG, PEXG, and elective cataract removal ... Full text Link to item Cite

A new method for selection of angular aqueous plexus cells from porcine eyes: a model for Schlemm's canal endothelium.

Journal Article Invest Ophthalmol Vis Sci · November 2010 PURPOSE: The authors sought to develop a technique for isolating and culturing angular aqueous plexus (AAP) cells from more plentiful porcine eyes. AAP is an analogue of Schlemm's canal. METHODS: Cells were differentially selected with puromycin, a toxin o ... Full text Link to item Cite

Cellular basis for bimatoprost effects on human conventional outflow.

Journal Article Invest Ophthalmol Vis Sci · October 2010 PURPOSE: Bimatoprost is a widely used ocular hypotensive agent to treat glaucoma. It lowers intraocular pressure in humans by increasing both pressure-independent (uveoscleral) and pressure-dependent (conventional) aqueous humor outflow. The present study ... Full text Link to item Cite

Induction of angiogenic immediate early genes by activation of FP prostanoid receptors in cultured human ciliary smooth muscle cells.

Journal Article Curr Eye Res · May 2010 PURPOSE: Agonists of the F prostanoid receptor for prostaglandin F2alpha exert. exert an ocular hypotensive effect that has been attributed to increased aqueous humor outflow through the uveoscleral pathway. Although tissue remodeling of the ciliary muscle ... Full text Link to item Cite

The biology of schlemm’s canal

Chapter · January 1, 2010 As aqueous humor drains, it is collected by a venous vessel, Schlemm’s canal, which encircles the eye at the corneoscleral junction. Apart from its role in returning aqueous humor to the systemic circulation, Schlemm’s canal participates in the generation ... Full text Cite

The biology of schlemm’s canal

Chapter · January 1, 2010 As aqueous humor drains, it is collected by a venous vessel, Schlemm’s canal, which encircles the eye at the corneoscleral junction. Apart from its role in returning aqueous humor to the systemic circulation, Schlemm’s canal participates in the generation ... Full text Cite

Drained secant modulus for human and porcine peripapillary sclera using unconfined compression testing.

Journal Article Exp Eye Res · December 2009 Glaucoma is an ocular disease characterized by damage of the optic nerve head (ONH) resulting in blindness. Recent research has identified the material properties of the sclera as being an important factor in the biomechanics of major load bearing tissues ... Full text Link to item Cite

Sphingosine-1-phosphate effects on the inner wall of Schlemm's canal and outflow facility in perfused human eyes.

Journal Article Exp Eye Res · December 2009 Previous work has shown that sphingosine 1-phosphate (S1P) decreases outflow facility in perfused porcine eyes while dramatically increasing giant vacuole density in the inner wall of the aqueous plexus, with no obvious changes in the trabecular meshwork ( ... Full text Link to item Cite

Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells.

Journal Article BMC Med Genomics · September 10, 2009 BACKGROUND: In addition to their well-documented ocular therapeutic effects, glucocorticoids (GCs) can cause sight-threatening side-effects including ocular hypertension presumably via morphological and biochemical changes in trabecular meshwork (TM) cells ... Full text Link to item Cite

Relationship between glaucoma and selenium levels in plasma and aqueous humour.

Journal Article Br J Ophthalmol · September 2009 AIM: The aim of the study was to compare selenium levels in plasma and aqueous humour in subjects with and without primary open-angle glaucoma (POAG). METHODS: Forty-seven POAG cases and 54 controls in this case-control study were recruited from surgery pa ... Full text Link to item Cite

PRDX6 attenuates oxidative stress- and TGFbeta-induced abnormalities of human trabecular meshwork cells.

Journal Article Free Radic Res · September 2009 Oxidative stress and TGFbeta-induced disturbance of cells and tissues are implicated in initiation and progression of pathophysiology of cells/tissues. Using primary human trabecular meshwork (TM) cells from normal and glaucomatous subjects, this study dem ... Full text Link to item Cite

Cyclic mechanical stress and trabecular meshwork cell contractility.

Journal Article Invest Ophthalmol Vis Sci · August 2009 PURPOSE: Ocular pulse decreases outflow facility of perfused anterior segments. However, the mechanism by which conventional outflow tissues respond to cyclic intraocular pressure oscillations is unknown. The purpose of the present study was to examine res ... Full text Link to item Cite

Role of aquaporin-1 in trabecular meshwork cell homeostasis during mechanical strain.

Journal Article Exp Eye Res · June 15, 2009 Aquaporin-1 (AQP1) channels are expressed by trabecular meshwork (TM) and Schlemm's canal cells of the conventional outflow pathway where fluid movement is predominantly paracellular, suggesting a non-canonical role for AQP1. We hypothesized that AQP1 func ... Full text Link to item Cite

The changing paradigm of outflow resistance generation: towards synergistic models of the JCT and inner wall endothelium.

Journal Article Exp Eye Res · April 2009 Aqueous humor outflow resistance is the primary determinant of intraocular pressure (IOP), and increased outflow resistance is the basis for elevated IOP associated with glaucoma. Experimental evidence suggests that the bulk of outflow resistance is genera ... Full text Link to item Cite

Regulation of myocilin-associated exosome release from human trabecular meshwork cells.

Journal Article Invest Ophthalmol Vis Sci · March 2009 PURPOSE: The goal of the present study was to determine whether the release of exosomes containing MYOC from trabecular meshwork (TM) cells is constitutive or regulated. METHODS: Conditioned media from TM cells were analyzed for MYOC-associated exosomes af ... Full text Link to item Cite

Enhanced inflow and outflow rates despite lower IOP in bestrophin-2-deficient mice.

Journal Article Invest Ophthalmol Vis Sci · February 2009 PURPOSE: Bestrophin-2 (Best2), a putative Cl(-) channel is expressed in the nonpigmented epithelium (NPE). Disruption of Best2 in mice results in a diminished intraocular pressure (IOP). Aqueous humor dynamics were compared in Best2(+/+) and Best2(-/-) mic ... Full text Link to item Cite

Aquaporin-1 expression and conventional aqueous outflow in human eyes.

Journal Article Exp Eye Res · October 2008 Aquaporin channels facilitate the enhanced permeability of secretory and absorptive tissues to water. In the conventional drainage tract, aquaporin-1 is expressed but its contribution to outflow facility is unknown. The purpose of the present study was to ... Full text Link to item Cite

L-DOPA is an endogenous ligand for OA1.

Journal Article PLoS Biol · September 30, 2008 Albinism is a genetic defect characterized by a loss of pigmentation. The neurosensory retina, which is not pigmented, exhibits pathologic changes secondary to the loss of pigmentation in the retina pigment epithelium (RPE). How the loss of pigmentation in ... Full text Link to item Cite

Endogenous Bioactive Lipids and the Regulation of Conventional Outflow Facility.

Journal Article Expert Rev Ophthalmol · 2008 Perturbation of paracrine signaling within the human conventional outflow pathway influences tissue homeostasis and outflow function. For example, exogenous introduction of the bioactive lipids, sphingosine-1-phosphate, anandamide or prostaglandin F(2α), t ... Full text Link to item Cite

Effects of cyclic intraocular pressure on conventional outflow facility.

Journal Article Invest Ophthalmol Vis Sci · January 2008 PURPOSE: In vivo, biomechanical stress plays an important role in tissue physiology and pathology, affecting cell and tissue behavior. Even though conventional outflow tissues are constantly exposed to dynamic changes in intraocular pressure, effects of su ... Full text Link to item Cite

Bimatoprost, prostamide activity, and conventional drainage.

Journal Article Invest Ophthalmol Vis Sci · September 2007 PURPOSE: Despite structural similarity with prostaglandin F(2 alpha), the ocular hypotensive agent bimatoprost (Lumigan; Allergan, Inc., Irvine, CA) shows unique pharmacology in vitro and functional activity in vivo. Unfortunately, the precise mechanisms t ... Full text Link to item Cite

Targeted gene transfer to Schlemm's canal by retroperfusion.

Journal Article Exp Eye Res · May 2007 The goal of the present study was to specifically modify protein expression in the resistance-generating region of the conventional outflow pathway, namely the inner wall of Schlemm's canal (SC) and the juxtacanalicular region of the trabecular meshwork, i ... Full text Link to item Cite

Myocilin-associated exosomes in human ocular samples.

Journal Article Exp Eye Res · January 2007 Mutations in myocilin result in ocular hypertension, likely due to decreased drainage of aqueous humor through the trabecular meshwork. Since less myocilin is found in the aqueous humor of those with disease-causing mutations, understanding myocilin's role ... Full text Link to item Cite

Schlemm's canal endothelia, lymphatic, or blood vasculature?

Journal Article J Glaucoma · 2007 In the human eye, the final barrier for aqueous humor to cross before returning to systemic circulation is the inner wall of Schlemm's canal. Unfortunately, the specific contribution of the inner wall to total outflow resistance in the conventional pathway ... Full text Link to item Cite

Coiled-coil targeting of myocilin to intracellular membranes.

Journal Article Exp Eye Res · December 2006 Mutations in myocilin (MYOC) associate with glaucoma and ocular hypertension. Unfortunately, the specific role of MYOC, a widely expressed protein of unknown function, in ocular hypertension is unknown. Since MYOC localizes both to intracellular membranes ... Full text Link to item Cite

Ion channel function of aquaporin-1 natively expressed in choroid plexus.

Journal Article J Neurosci · July 26, 2006 Aquaporins are known as water channels; however, an additional ion channel function has been observed for several including aquaporin-1 (AQP1). Using primary cultures of rat choroid plexus, a brain tissue that secretes CSF and abundantly expresses AQP1, we ... Full text Link to item Cite

Rate of change in central corneal thickness: a viability indicator for conventional drainage tissues in organ culture.

Journal Article Exp Eye Res · June 2006 Organ culture of human anterior segments is a powerful tool for understanding trabecular meshwork biology. However, data from a significant percentage of cultured anterior segments are unusable because tissues fail to meet quality control requirements, suc ... Full text Link to item Cite

Alterations in human trabecular meshwork cell homeostasis by selenium.

Journal Article Exp Eye Res · April 2006 Epidemiological evidence indicates that selenium supplementation may increase risk for glaucoma and ocular hypertension. The purpose of this study was to determine the effects of selenium on trabecular meshwork cells, a likely site of pathology for glaucom ... Full text Link to item Cite

Barriers to productive transfection of trabecular meshwork cells.

Journal Article Mol Vis · October 26, 2005 PURPOSE: A critical function of trabecular meshwork cells is to degrade cellular debris, including DNA. We hypothesize that low transfection efficiencies of primary human trabecular meshwork (HTM) cell cultures with plasmid DNA are a function of retained c ... Link to item Cite

Extracellular trafficking of myocilin in human trabecular meshwork cells.

Journal Article J Biol Chem · August 12, 2005 Myocilin (MYOC) is a protein with a broad expression pattern, but unknown function. MYOC associates with intracellular structures that are consistent with secretory vesicles, however, in most cell types studied, MYOC is limited to the intracellular compart ... Full text Link to item Cite

Differential P1-purinergic modulation of human Schlemm's canal inner-wall cells.

Journal Article Am J Physiol Cell Physiol · April 2005 Intraocular pressure is directly dependent on aqueous humor flow into, and resistance to flow out of, the eye. Adenosine has complex effects on intraocular pressure. Stimulation of A1 and A2A adenosine receptors changes intraocular pressure oppositely, lik ... Full text Link to item Cite

Specific targeting of gene expression to a subset of human trabecular meshwork cells using the chitinase 3-like 1 promoter.

Journal Article Invest Ophthalmol Vis Sci · January 2005 PURPOSE: To compare the gene expression profile of trabecular meshwork (TM) and Schlemm's canal (SC) primary cultures and to identify promoters for targeting gene expression to specific cells in the outflow pathway. METHODS: The differential gene expressio ... Full text Link to item Cite

Effect of hydrostatic pressure gradients and Na2EDTA on permeability of human Schlemm's canal cell monolayers.

Journal Article Curr Eye Res · June 2004 PURPOSE: Elevated intraocular pressure in those with glaucoma appears to be a function of increased resistance to movement of aqueous humor through the conventional outflow pathway. The majority of resistance in both normal and glaucomatous eyes is generat ... Full text Link to item Cite

Experimental and numerical studies of adenovirus delivery to outflow tissues of perfused human anterior segments.

Journal Article Invest Ophthalmol Vis Sci · June 2004 PURPOSE: To investigate the efficacy of two different methods of adenoviral transfer of genes to trabecular meshwork (TM) and Schlemm's canal (SC) cells in cultured human anterior segments, using both experimental and numerical analyses. METHODS: Replicati ... Full text Link to item Cite

Expression analysis of the matrix GLA protein and VE-cadherin gene promoters in the outflow pathway.

Journal Article Invest Ophthalmol Vis Sci · May 2004 PURPOSE: To test the ability of promoter fragments from the matrix Gla protein (MGP) and vascular endothelial-cadherin (VE-cad) genes to target gene expression in a specific manner in the cells of the outflow pathway, by using adenoviral-mediated gene tran ... Full text Link to item Cite

Selenium's effects on MMP-2 and TIMP-1 secretion by human trabecular meshwork cells.

Journal Article Invest Ophthalmol Vis Sci · February 2004 PURPOSE: Because of the observed increase in incidence of glaucoma among some individuals taking selenium as a dietary supplement, the present study was undertaken to investigate mechanisms of selenium-induced changes in homeostasis of human trabecular mes ... Full text Link to item Cite

Aquaporin-1 channels in human retinal pigment epithelium: role in transepithelial water movement.

Journal Article Invest Ophthalmol Vis Sci · June 2003 PURPOSE: Aquaporin (AQP) is a hexahelical integral membrane protein that functions as a constitutive channel for water and regulated channel for cations in fluid transporting tissues, including many in the eye. Although AQP1 has been cloned from a cDNA lib ... Full text Link to item Cite

Common actions of adenosine receptor agonists in modulating human trabecular meshwork cell transport.

Journal Article J Membr Biol · May 15, 2003 A(1) adenosine receptors (ARs) reduce, and A(2)ARs increase intraocular pressure, partly by differentially altering resistance to aqueous humor outflow. It is unknown whether the opposing effects of A(1)AR and A(2)AR agonists are mediated at different outf ... Full text Link to item Cite

Alpha-2 adrenergic receptors stimulate actin organization in developing fetal rat cardiac myocytes.

Journal Article Life Sci · February 14, 2003 Expression of alpha(2)-adrenergic receptors (alpha(2)-AR) is very high in fetal rat heart although numbers decline with increasing gestational age. The current experiments were designed to identify the subtypes of alpha(2)-AR expressed and the function of ... Full text Link to item Cite

Human Schlemm's canal cells express the endothelial adherens proteins, VE-cadherin and PECAM-1.

Journal Article Curr Eye Res · November 2002 Purpose. The majority of resistance to outflow of aqueous humor resides at or near the inner wall of Schlemm's canal (SC). Transmembrane proteins that contribute to the generation of resistance to aqueous outflow likely participate in junctional complexes ... Full text Link to item Cite

Human trabecular meshwork cell volume regulation.

Journal Article Am J Physiol Cell Physiol · July 2002 The volume of certain subpopulations of trabecular meshwork (TM) cells may modify outflow resistance of aqueous humor, thereby altering intraocular pressure. This study examines the contribution that Na+/H+, Cl-/HCO exchange, and K+-Cl- efflux mechanisms h ... Full text Link to item Cite

Expression of alpha(2)-adrenergic receptor subtypes in prenatal rat spinal cord.

Journal Article Brain Res Dev Brain Res · February 28, 2002 The results of molecular cloning have revealed three subtypes of the alpha(2)-adrenergic receptors (alpha(2) AR) that have been defined alpha(2)C10 (alpha(2A)), alpha(2)C2 (alpha(2B)) and alpha(2)C4 (alpha(2C)). The differential expression of alpha(2) AR s ... Full text Link to item Cite

Tetraethylammonium block of water flux in Aquaporin-1 channels expressed in kidney thin limbs of Henle's loop and a kidney-derived cell line.

Journal Article BMC Physiol · 2002 BACKGROUND: Aquaporin-1 (AQP1) channels are constitutively active water channels that allow rapid transmembrane osmotic water flux, and also serve as cyclic-GMP-gated ion channels. Tetraethylammonium chloride (TEA; 0.05 to 10 mM) was shown previously to in ... Full text Link to item Cite

Cannabinoid CB(1) receptor expression, activation and detection of endogenous ligand in trabecular meshwork and ciliary process tissues.

Journal Article Eur J Pharmacol · November 23, 2001 Elevated intraocular pressure is the primary risk factor for glaucoma. Cannabinoids interact with molecular targets in the eye and lower intraocular pressure by an unknown mechanism. The purpose of the present study was to examine eye tissues for functiona ... Full text Link to item Cite

Expression of aquaporin-1 in human trabecular meshwork cells: role in resting cell volume.

Journal Article Invest Ophthalmol Vis Sci · July 2001 PURPOSE: Drainage of aqueous humor from the human eye appears dependent on intracellular volume of trabecular meshwork (TM) cells, the predominant cell type of the human outflow pathway. Thus, the modulation of water and solute flux across the plasma membr ... Link to item Cite

Effect of AQP1 expression level on Co(2) permeability in bovine corneal endothelium.

Journal Article Invest Ophthalmol Vis Sci · February 2001 PURPOSE: Corneal endothelial fluid transport is dependent on HCO(3)(-) and CO(2) fluxes. CO(2) permeability (P:CO(2)) measurements in an oocyte expression system and in reconstituted proteoliposomes have suggested that the water channel AQP1 can transport ... Link to item Cite

Isolation of primary open-angle glaucomatous trabecular meshwork cells from whole eye tissue.

Journal Article Curr Eye Res · May 2000 PURPOSE: Isolation and culture of human trabecular meshwork (TM) cells from primary open-angle glaucomatous (POAG) tissue has proven difficult. The objective of this study was to directly compare the utility of two different isolation methods to obtain via ... Link to item Cite

Hydraulic pressure stimulates adenosine 3',5'-cyclic monophosphate accumulation in endothelial cells from Schlemm's canal.

Journal Article Invest Ophthalmol Vis Sci · August 1999 PURPOSE: Fluid flow across various endothelia results in a variety of intracellular and extracellular adaptations. In the living eye, aqueous humor flows across the surface of endothelial cells on trabecular meshwork (TM) beams and in the juxtacanalicular ... Link to item Cite

Isolation, culture, and characterization of endothelial cells from Schlemm's canal.

Journal Article Invest Ophthalmol Vis Sci · September 1998 PURPOSE: An important goal in glaucoma research has been to understand the functional contribution of trabecular meshwork (TM) and Schlemm's canal (SC) endothelia to aqueous humor outflow resistance. To date, TM cells are routinely cultured and used as a m ... Link to item Cite

Prostaglandin F2 alpha receptors in the human trabecular meshwork.

Journal Article Invest Ophthalmol Vis Sci · February 1998 PURPOSE: Prostaglandin F2 alpha (PGF2 alpha) and analogs, such as latanoprost, are thought to lower intraocular pressure (IOP), primarily by increasing uveoscleral outflow. However, outflow through the trabecular meshwork may be increased as well. The auth ... Link to item Cite

Aquaporins and ion conductance.

Other Science · March 7, 1997 Link to item Cite

Characterization of the transmembrane orientation of aquaporin-1 using antibodies to recombinant fusion proteins.

Journal Article Biochemistry · December 17, 1996 Aquaporin-1 (AQP1) is a member of a family of integral membrane proteins, the aquaporins, which function as molecular channels for the movement of water across the plasma membrane. While the primary structure of AQP1 has been obtained from the cloning of i ... Full text Link to item Cite

Cultured human trabecular meshwork cells express functional alpha 2A adrenergic receptors.

Journal Article Invest Ophthalmol Vis Sci · November 1996 PURPOSE: For the treatment of glaucoma, alpha-2 adrenergic receptor (alpha 2-AR) agonists are thought to lower intraocular pressure primarily by decreasing aqueous humor production. Effects on the outflow pathways, however, also may occur. To begin to exam ... Link to item Cite

Forskolin stimulation of water and cation permeability in aquaporin 1 water channels.

Journal Article Science · August 30, 1996 Aquaporin 1, a six-transmembrane domain protein, is a water channel present in many fluid-secreting and -absorbing cells. In Xenopus oocytes injected with aquaporin 1 complementary RNA, the application of forskolin or cyclic 8-bromo- adenosine 3',5'-monoph ... Full text Link to item Cite

Activation of α2A-adrenergic receptors in human trabecular meshwork cells stimulates MAP kinase activity

Conference Investigative Ophthalmology and Visual Science · February 15, 1996 Purpose: Previously, we have demonstrated the presence of α2A-adrenergic receptors (AR) in primary cultures of human trabecular meshwork (HTM) cells by immunofluorescence microscopy and the inhibition of forskolin-stimulated adenylyl cyclase. Since it has ... Cite

Cultured human trabecular meshwork cells express aquaporin-1 water channels.

Journal Article Curr Eye Res · December 1995 The identification and characterization of aquaporin-1 water channels and other related proteins has provided a molecular explanation for the enhanced permeability of a variety of epithelial tissues. Previously, we documented the distribution of aquaporin- ... Full text Link to item Cite

Localization of alpha 2-adrenergic receptor subtypes in the anterior segment of the human eye with selective antibodies.

Journal Article Invest Ophthalmol Vis Sci · December 1995 PURPOSE: To develop antibodies that selectively recognize each of the alpha 2-adrenergic receptor (AR) subtypes and to determine the expression and localization of these subtypes in the anterior segment of the human eye. METHODS: Recent studies have shown ... Link to item Cite

Isolation and culture of human trabecular meshwork cells by extracellular matrix digestion.

Journal Article Curr Eye Res · July 1995 Like corneal endothelial cells, human trabecular meshwork cells are believed to be of neural crest origin, but demonstrate physiological properties and an antithrombogenic surface similar to vascular endothelial cells. One current method for isolating trab ... Full text Link to item Cite

Localization of aquaporin CHIP in the human eye: implications in the pathogenesis of glaucoma and other disorders of ocular fluid balance.

Journal Article Invest Ophthalmol Vis Sci · October 1994 PURPOSE: The existence of integral membrane proteins that serve as selective water channels has been postulated to explain the movement of water across plasma membranes. Aquaporin CHIP (channel-forming integral membrane protein of 28 kd) is the first such ... Link to item Cite

Dexamethasone decreases tissue plasminogen activator activity in trabecular meshwork organ and cell cultures.

Journal Article J Glaucoma · 1994 Previously, we observed that dexamethasone decreased the extracellular activity of some matrix metalloproteinases and tissue plasminogen activator in trabecular meshwork containing organ explants and cell cultures. We have extended these studies to determi ... Link to item Cite