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Rupalatha Maddala

Assistant Professor of Ophthalmology
Ophthalmology
Box 3802 Med Ctr, 4028 Aeri Building, 2351 Erwin Rd, Durham, NC 27710
2351 Erwin Road, 4028 Aeri Building, Durham, NC 27710

Selected Publications


Protocol for the Extraction and Characterization of Trabecular Meshwork Cell Cytoskeleton Fraction.

Journal Article Methods Mol Biol · 2025 Among various cellular attributes modulating aqueous humor (AH) outflow through the trabecular pathway and eventually intraocular pressure, the involvement of actomyosin regulated cellular contraction and relaxation, cell-extracellular matrix adhesion and ... Full text Link to item Cite

Influence of Growth Differentiation Factor 15 on Intraocular Pressure in Mice.

Journal Article Lab Invest · April 2024 Growth differentiation factor 15 (GDF15), a stress-sensitive cytokine, and a distant member of the transforming growth factor β superfamily, has been shown to exhibit increased levels with aging, and in various age-related pathologies. Although GDF15 level ... Full text Link to item Cite

Influence of the calcium voltage-gated channel auxiliary subunit (CACNA2D1) absence on intraocular pressure in mice.

Journal Article Exp Eye Res · April 2024 The etiology of elevated intraocular pressure (IOP), a major risk factor for glaucoma (optic nerve atrophy), is poorly understood despite continued efforts. Although the gene variant of CACNA2D1 (encoding α2δ1), a calcium voltage-gated channel auxiliary su ... Full text Link to item Cite

Glypican-4 regulated actin cytoskeletal reorganization in glucocorticoid treated trabecular meshwork cells and involvement of Wnt/PCP signaling.

Journal Article J Cell Physiol · March 2023 A common adverse response to the clinical use of glucocorticoids (GCs) is elevated intraocular pressure (IOP) which is a major risk factor for glaucoma. Elevated IOP arises due to impaired outflow of aqueous humor (AH) through the trabecular meshwork (TM). ... Full text Link to item Cite

Mechanical Load and Piezo1 Channel Regulated Myosin II Activity in Mouse Lenses.

Journal Article Int J Mol Sci · April 24, 2022 The cytoarchitecture and tensile characteristics of ocular lenses play a crucial role in maintaining their transparency and deformability, respectively, which are properties required for the light focusing function of ocular lens. Calcium-dependent myosin- ... Full text Link to item Cite

Role of vasorin, an anti-apoptotic, anti-TGF-β and hypoxia-induced glycoprotein in the trabecular meshwork cells and glaucoma.

Journal Article J Cell Mol Med · April 2022 Glaucoma, one of the leading causes of irreversible blindness, is commonly associated with elevated intraocular pressure due to impaired aqueous humour (AH) drainage through the trabecular meshwork. The aetiological mechanisms contributing to impaired AH o ... Full text Link to item Cite

Elevated Levels of Growth/Differentiation Factor-15 in the Aqueous Humor and Serum of Glaucoma Patients.

Journal Article J Clin Med · January 29, 2022 Dysregulated levels of growth/differentiation factor-15 (GDF15), a divergent member of the transforming growth factor-beta super family, have been found to be associated with the pathology of various diseases. In this study, we evaluated the levels of GDF1 ... Full text Link to item Cite

Glucocorticoids Preferentially Influence Expression of Nucleoskeletal Actin Network and Cell Adhesive Proteins in Human Trabecular Meshwork Cells.

Journal Article Front Cell Dev Biol · 2022 Clinical use of glucocorticoids is associated with increased intraocular pressure (IOP), a major risk factor for glaucoma. Glucocorticoids have been reported to induce changes in actin cytoskeletal organization, cell adhesion, extracellular matrix, fibroge ... Full text Open Access Link to item Cite

Drebrin, an actin-binding protein, is required for lens morphogenesis and growth.

Journal Article Dev Dyn · November 2021 BACKGROUND: Lens morphogenesis, architecture, and clarity are known to be critically dependent on actin cytoskeleton organization and cell adhesive interactions. There is limited knowledge, however regarding the identity and role of key proteins regulating ... Full text Link to item Cite

Absence of S100A4 in the mouse lens induces an aberrant retina-specific differentiation program and cataract.

Journal Article Sci Rep · January 26, 2021 S100A4, a member of the S100 family of multifunctional calcium-binding proteins, participates in several physiological and pathological processes. In this study, we demonstrate that S100A4 expression is robustly induced in differentiating fiber cells of th ... Full text Open Access Link to item Cite

Global phosphotyrosinylated protein profile of cell-matrix adhesion complexes of trabecular meshwork cells.

Journal Article Am J Physiol Cell Physiol · August 1, 2020 Dysregulation of the mechanical properties and cell adhesive interactions of trabecular meshwork (TM) are known to impair aqueous humor drainage and elevate intraocular pressure in glaucoma patients. The identity of regulatory mechanisms underlying TM mech ... Full text Link to item Cite

Calponin-3 deficiency augments contractile activity, plasticity, fibrogenic response and Yap/Taz transcriptional activation in lens epithelial cells and explants.

Journal Article Sci Rep · January 28, 2020 The transparent ocular lens plays a crucial role in vision by focusing light on to the retina with loss of lens transparency leading to impairment of vision. While maintenance of epithelial phenotype is recognized to be essential for lens development and f ... Full text Link to item Cite

Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth.

Journal Article Dev Biol · February 1, 2019 Epithelial cell polarity, adhesion, proliferation, differentiation and survival are essential for morphogenesis of various organs and tissues including the ocular lens. The molecular mechanisms regulating the lens epithelial phenotype however, are not well ... Full text Link to item Cite

Vertebrate Lonesome Kinase Regulated Extracellular Matrix Protein Phosphorylation, Cell Shape, and Adhesion in Trabecular Meshwork Cells.

Journal Article J Cell Physiol · September 2017 Glaucoma, a leading cause of irreversible blindness, is commonly associated with elevated intraocular pressure (IOP) due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM). Although dysregulated production and organization of extr ... Full text Link to item Cite

Switching of α-Catenin From Epithelial to Neuronal Type During Lens Epithelial Cell Differentiation.

Journal Article Invest Ophthalmol Vis Sci · July 1, 2017 PURPOSE: Ocular lens fiber cell elongation, differentiation, and compaction are associated with extensive reorganization of cell adhesive interactions and cytoskeleton; however, our knowledge of proteins critical to these events is still evolving. This stu ... Full text Link to item Cite

Corneal Endothelial Cell Migration and Proliferation Enhanced by Rho Kinase (ROCK) Inhibitors in In Vitro and In Vivo Models.

Journal Article Invest Ophthalmol Vis Sci · December 1, 2016 PURPOSE: To explore the role of Rho-associated kinases (ROCK) in corneal physiology and regeneration, and the effects of suppressing its activity in stimulating corneal endothelial cell proliferation and migration in vitro and in vivo. METHODS: Immunohisto ... Full text Link to item Cite

Growth Differentiation Factor-15-Induced Contractile Activity and Extracellular Matrix Production in Human Trabecular Meshwork Cells.

Journal Article Invest Ophthalmol Vis Sci · December 1, 2016 PURPOSE: To determine the role and regulation of growth differentiation factor-15 (GDF-15), a TGF-β-related cytokine in human trabecular meshwork (TM) cells in the context of aqueous humor (AH) outflow and IOP. METHODS: Regulation of expression by external ... Full text Link to item Cite

Ankyrin-B directs membrane tethering of periaxin and is required for maintenance of lens fiber cell hexagonal shape and mechanics.

Journal Article Am J Physiol Cell Physiol · January 15, 2016 Periaxin (Prx), a PDZ domain protein expressed preferentially in myelinating Schwann cells and lens fibers, plays a key role in membrane scaffolding and cytoarchitecture. Little is known, however, about how Prx is anchored to the plasma membrane. Here we r ... Full text Link to item Cite

Ankyrin-B in lens architecture and biomechanics: Just not tethering but more.

Journal Article Bioarchitecture · 2016 The ankyrins are a family of well-characterized metazoan adaptor proteins that play a key role in linking various membrane-spanning proteins to the underlying spectrin-actin cytoskeleton; a mechanistic understanding of their role in tissue architecture and ... Full text Link to item Cite

Rap1 GTPase is required for mouse lens epithelial maintenance and morphogenesis.

Journal Article Dev Biol · October 1, 2015 Rap1, a Ras-like small GTPase, plays a crucial role in cell-matrix adhesive interactions, cell-cell junction formation, cell polarity and migration. The role of Rap1 in vertebrate organ development and tissue architecture, however, remains elusive. We addr ... Full text Link to item Cite

Regulation of plasticity and fibrogenic activity of trabecular meshwork cells by Rho GTPase signaling.

Journal Article J Cell Physiol · July 2014 Glaucoma, a prevalent blinding disease is commonly associated with increased intraocular pressure due to impaired aqueous humor (AH) drainage through the trabecular meshwork (TM). Although increased TM tissue contraction and stiffness in association with a ... Full text Link to item Cite

Effects of Y27632 on keratinocyte procurement and wound healing.

Journal Article Clin Exp Dermatol · October 2013 A number of Rho-kinase inhibitors have been developed for various clinical applications. We examined the effects of the Rho-kinase inhibitor Y27632 on keratinocyte proliferation and migration, and found that it promoted primary human keratinocyte prolifera ... Full text Link to item Cite

L-type calcium channels play a critical role in maintaining lens transparency by regulating phosphorylation of aquaporin-0 and myosin light chain and expression of connexins.

Journal Article PLoS One · 2013 Homeostasis of intracellular calcium is crucial for lens cytoarchitecture and transparency, however, the identity of specific channel proteins regulating calcium influx within the lens is not completely understood. Here we examined the expression and distr ... Full text Link to item Cite

Connective tissue growth factor-mediated upregulation of neuromedin U expression in trabecular meshwork cells and its role in homeostasis of aqueous humor outflow.

Journal Article Invest Ophthalmol Vis Sci · July 26, 2012 PURPOSE: Connective tissue growth factor (CTGF) is a matricellular protein presumed to be involved in the pathobiology of various fibrotic diseases, including glaucoma. We investigated the effects of Rho GTPase-dependent actin cytoskeletal integrity on CTG ... Full text Link to item Cite

Rac1 GTPase-deficient mouse lens exhibits defects in shape, suture formation, fiber cell migration and survival.

Journal Article Dev Biol · December 1, 2011 Morphogenesis and shape of the ocular lens depend on epithelial cell elongation and differentiation into fiber cells, followed by the symmetric and compact organization of fiber cells within an enclosed extracellular matrix-enriched elastic capsule. The ce ... Full text Link to item Cite

Periaxin is required for hexagonal geometry and membrane organization of mature lens fibers.

Journal Article Dev Biol · September 1, 2011 Transparency of the ocular lens depends on symmetric packing and membrane organization of highly elongated hexagonal fiber cells. These cells possess an extensive, well-ordered cortical cytoskeleton to maintain cell shape and to anchor membrane components. ... Full text Link to item Cite

Characterization of cytoskeleton-enriched protein fraction of the trabecular meshwork and ciliary muscle cells.

Journal Article Invest Ophthalmol Vis Sci · December 2010 PURPOSE: To understand the molecular basis for the known distinct contractile characteristics of trabecular meshwork (TM) and ciliary muscle (CM) cells, the cytoskeleton-enriched protein fractions of the TM and CM cells were isolated and characterized. MET ... Full text Link to item Cite

Abundant expression of ponsin, a focal adhesion protein, in lens and downregulation of its expression by impaired cytoskeletal signaling.

Journal Article Invest Ophthalmol Vis Sci · April 2009 PURPOSE: This study was undertaken to improve understanding of the defective lens developmental changes induced by the transgenic overexpression of the Rho GDP dissociation inhibitor RhoGDIalpha. The study was focused on a single differentially expressed g ... Full text Link to item Cite

Novel molecular insights into RhoA GTPase-induced resistance to aqueous humor outflow through the trabecular meshwork.

Journal Article Am J Physiol Cell Physiol · November 2008 Impaired drainage of aqueous humor through the trabecular meshwork (TM) culminating in increased intraocular pressure is a major risk factor for glaucoma, a leading cause of blindness worldwide. Regulation of aqueous humor drainage through the TM, however, ... Full text Link to item Cite

Characterization of lens fiber cell triton insoluble fraction reveals ERM (ezrin, radixin, moesin) proteins as major cytoskeletal-associated proteins.

Journal Article Biochem Biophys Res Commun · April 11, 2008 To understand lens fiber cell elongation- and differentiation-associated cytoskeletal remodeling, here we identified and characterized the major protein components of lens fiber cell Triton X-100 insoluble fraction by mass spectrometry and immunoblot analy ... Full text Link to item Cite

Rho GDP dissociation inhibitor-mediated disruption of Rho GTPase activity impairs lens fiber cell migration, elongation and survival.

Journal Article Dev Biol · March 1, 2008 To explore the role of the Rho GTPases in lens morphogenesis, we overexpressed bovine Rho GDP dissociation inhibitor (Rho GDI alpha), which serves as a negative regulator of Rho, Rac and Cdc42 GTPase activity, in a lens-specific manner in transgenic mice. ... Full text Link to item Cite

Lens fiber cell elongation and differentiation is associated with a robust increase in myosin light chain phosphorylation in the developing mouse.

Journal Article Differentiation · October 2007 Myosin II, a molecular motor, plays a critical role in cell migration, cell shape changes, cell adhesion, and cytokinesis. To understand the role of myosin II in lens fiber cell elongation and differentiation, we determined the distribution pattern of nonm ... Full text Link to item Cite

Influence of actin cytoskeletal integrity on matrix metalloproteinase-2 activation in cultured human trabecular meshwork cells.

Journal Article Invest Ophthalmol Vis Sci · May 2007 PURPOSE: The goal of this study was to investigate the possible link between actin cytoskeletal integrity and the activation of matrix metalloproteinases (MMPs) in trabecular meshwork (TM) cells. METHODS: Primary human TM (HTM) cells treated with different ... Full text Link to item Cite

The role of the lens actin cytoskeleton in fiber cell elongation and differentiation.

Journal Article Semin Cell Dev Biol · December 2006 The vertebrate ocular lens is a fascinating and unique transparent tissue that grows continuously throughout life. During the process of differentiation into fiber cells, lens epithelial cells undergo dramatic morphological changes, membrane remodeling, po ... Full text Link to item Cite

Regulation of connective tissue growth factor expression in the aqueous humor outflow pathway.

Journal Article Mol Vis · September 30, 2006 PURPOSE: Connective Tissue Growth Factor (CTGF) is an inducible secretory protein known to regulate proliferation and extracellular matrix production in various cell types. We hypothesize that CTGF plays a critical role in the physiological regulation of a ... Link to item Cite

alpha-Crystallin localizes to the leading edges of migrating lens epithelial cells.

Journal Article Exp Cell Res · May 15, 2005 alpha-crystallin (alphaA and alphaB) is a major lens protein, which belongs to the small heat-shock family of proteins and binds to various cytoskeletal proteins including actin, vimentin and desmin. In this study, we investigated the cellular localization ... Full text Link to item Cite

Expression of dominant negative Rho-binding domain of Rho-kinase in organ cultured human eye anterior segments increases aqueous humor outflow.

Journal Article Mol Vis · April 27, 2005 PURPOSE: Based on pharmacological inhibition of activity, a role has been proposed for Rho-kinase in the modulation of aqueous outflow and intraocular pressure (IOP). This study employed a molecular approach to specifically address the role of Rho-kinase i ... Link to item Cite

Impaired cytoskeletal organization and membrane integrity in lens fibers of a Rho GTPase functional knockout transgenic mouse.

Journal Article Lab Invest · June 2004 To investigate the effects of Rho GTPase inactivation on lens fiber cell cytoskeletal and morphological integrity, a transgenic mouse model expressing C3-exoenzyme (a bacterial toxin) in a lens-specific manner was utilized. Cryosections of whole eyes from ... Full text Link to item Cite

Expression of nonphagocytic NADPH oxidase system in the ocular lens.

Journal Article Mol Vis · February 19, 2004 PURPOSE: The primary goal of this study was to characterize the Rac GTPase associated, NADPH oxidase-mediated Reactive Oxygen Species (ROS)-generating system in the lens tissue. METHODS: NADPH oxidase activity in lens tissue was determined by quantifying s ... Link to item Cite

Growth factor induced activation of Rho and Rac GTPases and actin cytoskeletal reorganization in human lens epithelial cells.

Journal Article Mol Vis · July 17, 2003 PURPOSE: To determine the involvement of the Rho GTPases-mediated signaling pathway in growth factor-stimulated actomyosin cytoskeletal organization and focal adhesion formation in lens epithelial cells. METHODS: Serum starved human lens epithelial cells ( ... Link to item Cite

Inhibition of Rho-kinase induces alphaB-crystallin expression in lens epithelial cells.

Journal Article Biochem Biophys Res Commun · June 28, 2002 The small heat shock protein, alphaB-crystallin, has been shown to interact with actin and intermediate filament proteins. However, little is known regarding the cellular mechanisms regulating such interactions. In this study, we explored the role of the R ... Full text Link to item Cite

Selective expression of the small GTPase RhoB in the early developing mouse lens.

Journal Article Dev Dyn · November 2001 This report describes the expression and distribution pattern of RhoB GTPase in the developing mouse lens. RhoB expression was confirmed by sequencing an reverse transcriptase-polymerase chain reaction-generated DNA fragment of RhoB. Immunohistochemical an ... Full text Link to item Cite

Lovastatin-induced cytoskeletal reorganization in lens epithelial cells: role of Rho GTPases.

Journal Article Invest Ophthalmol Vis Sci · October 2001 PURPOSE: To understand the involvement of isoprenylated small guanosine triphosphatases (GTPases) in lovastatin-induced cataractogenesis, Rho- and Rac-mediated cell adhesion and actin cytoskeletal reorganization were investigated in lovastatin-treated lens ... Link to item Cite