Journal ArticleJ Biol Chem · September 2025
Mutations in the mitochondrial respiratory complex I accessory subunit NADH:ubiquinone oxidoreductase subunit S4 (ndufs4) can cause the mitochondrial disease Leigh syndrome, which may be associated with vision loss. We previously demonstrated that mice wit ...
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Journal ArticleExp Eye Res · May 2025
Age-related macular degeneration (AMD) is a complex, multifactorial retinal degenerative disease that is influenced by both genetic and environmental factors. However, the strongest risk factor for AMD is advanced age. Several physiological processes are o ...
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Journal ArticleAdv Exp Med Biol · 2025
The underlying mechanisms associated with age-related changes in the morphology and function of retinal pigmented epithelial (RPE) cells are poorly understood. The aging RPE progresses through several structural changes including loss of melanin granules, ...
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Chapter · January 1, 2025
The retinal pigment epithelium plays a pivotal role in retinal health and function. It however does not work in isolation, rather it collaborates closely with adjacent tissues, including the photoreceptors on the apical side and Bruch's membrane and the ch ...
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Journal ArticleSTAR Protoc · September 20, 2024
During aging and in retinal degenerative diseases, vulnerable retinal pigment epithelial (RPE) cells are subject to mitochondrial dysfunction, creating a need for accessibility to tools which can facilitate assessment of the ocular posterior pole bioenerge ...
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Journal ArticleCurr Opin Pharmacol · April 2024
To develop effective therapies for complex blinding diseases such as age-related macular degeneration (AMD), identification of mechanisms involved in its initiation and progression is needed. The estrogen-related receptor alpha (ESRRA) is an orphan nuclear ...
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Journal ArticleProg Retin Eye Res · May 2023
The functions and activities of nuclear receptors, the largest family of transcription factors in the human genome, have classically focused on their ability to act as steroid and hormone sensors in endocrine organs. However, they are responsible for a div ...
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Journal ArticleJ Ocul Pharmacol Ther · May 2023
Purpose: Angiotensin-(1-12) [Ang-(1-12)] serves as a primary substrate to generate angiotensin II (Ang II) by angiotensin-converting enzyme and/or chymase suggests it may be an unrecognized source of Ang II-mediated microvascular complication in hypertensi ...
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Journal ArticleAdv Exp Med Biol · 2023
Age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly in developed countries. It is a complex, multifactorial, progressive disease with diverse molecular pathways, including inflammation, regulating its pathogenesi ...
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Journal ArticleFront Ophthalmol (Lausanne) · 2023
Adult-onset foveomacular dystrophy (AOFVD) is a retinal pattern dystrophy that may affect up to 1 in 7,400 individuals. There is much that is unknown regarding this disease's epidemiology, risk factors for development, and rate of progression through its f ...
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Journal ArticleExp Eye Res · December 2022
Advanced age is the most established risk factor for developing age-related macular degeneration (AMD), one of the leading causes of visual impairment in the elderly, in Western and developed countries. Similarly, after middle age, there is an exponential ...
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Journal ArticleLab Invest · October 2022
Apolipoprotein B100 (apoB100) is the structural protein of cholesterol carriers including low-density lipoproteins. It is a constituent of sub-retinal pigment epithelial (sub-RPE) deposits and pro-atherogenic plaques, hallmarks of early dry age-related mac ...
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Journal ArticleLab Invest · October 2022
Apolipoprotein B100 (apoB100) is the structural protein of cholesterol carriers including low-density lipoproteins. It is a constituent of sub-retinal pigment epithelial (sub-RPE) deposits and pro-atherogenic plaques, hallmarks of early dry age-related mac ...
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Journal ArticleExp Eye Res · September 2022
Age-related macular degeneration (AMD) is a disease that affects the macula - the central part of the retina. It is a leading cause of irreversible vision loss in the elderly. AMD onset is marked by the presence of lipid- and protein-rich extracellular dep ...
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Journal ArticleCells · August 2, 2022
The choroid is a vulnerable tissue site in the eye, impacted in several blinding diseases including age related macular degeneration (AMD), which is the leading cause of central vision loss in the aging population. Choroidal thinning and choriocapillary dr ...
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Journal ArticleProc Natl Acad Sci U S A · July 12, 2022
Phenotypic variations in the retinal pigment epithelial (RPE) layer are often a predecessor and driver of ocular degenerative diseases, such as age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We previously identifie ...
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Journal ArticleJ Ocul Pharmacol Ther · June 2022
Purpose: The NLRP3 inflammasome, a cytoplasmic signal transduction complex that regulates inflammation, has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of visual impairment in industrialized countries. W ...
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Journal ArticleFASEB J · May 2022
INTRODUCTION: The characterization, by this laboratory, of angiotensin-(1-12) [Ang-(1-12)] as a primary angiotensin II (Ang II)-forming substrate may be an unrecognized source of Ang II-mediated microvascular complication in hypertension-mediated retinopat ...
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Journal ArticleFASEB J · May 2022
PURPOSE: Retinal pigmented epithelium (RPE) dysfunction is associated with age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the western world. A better understanding of RPE-related signaling pathways is the key to ...
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Journal ArticleMod Pathol · February 2022
A common clinical phenotype of several neurodegenerative and systemic disorders including Alzheimer's disease and atherosclerosis is the abnormal accumulation of extracellular material, which interferes with routine cellular functions. Similarly, patients ...
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Journal ArticleOphthalmol Sci · September 2021
PURPOSE: Micrometer-sized spherules formed of hydroxyapatite or whitlockite were identified within extracellular deposits that accumulate in the space between the basal lamina (BL) of retinal pigment epithelium (RPE) and the inner collagenous layer of Bruc ...
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Journal ArticleInt J Mol Sci · September 16, 2020
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which senses environmental, dietary or metabolic signals to mount a transcriptional response, vital in health and disease. As environmental stimuli and metabolic products have ...
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Journal ArticleInvest Ophthalmol Vis Sci · June 3, 2020
We live in an age where new technologies, and organizations involved in the distribution of biological materials, such as cell culture lines, have eased accessibility to a variety of in vitro models, developed, and/or harvested from different sources. In t ...
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Journal ArticleInt J Mol Sci · April 21, 2020
Vasculogenesis and angiogenesis are physiological mechanisms occurring throughout the body. Any disruption to the precise balance of blood vessel growth necessary to support healthy tissue, and the inhibition of abnormal vessel sprouting has the potential ...
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Journal ArticleJCI Insight · January 16, 2020
Effective treatments and animal models for the most prevalent neurodegenerative form of blindness in elderly people, called age-related macular degeneration (AMD), are lacking. Genome-wide association studies have identified lipid metabolism and inflammati ...
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Chapter · January 1, 2020
Age-related macular degeneration is the leading cause of vision loss in the elderly in the developed world, with an ever-increasing prevalence in the developing world. The complexity of the disease and lack of effective therapies speak to the necessity of ...
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Journal ArticleFront Cell Dev Biol · 2020
Age-related macular degeneration (AMD) is a neurodegenerative disease of the aging retina, in which patients experience severe vision loss. Therapies available to patients are limited and are only effective in a sub-population of patients. Future comprehen ...
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Journal ArticleAdv Exp Med Biol · 2019
Age-related macular degeneration (AMD) continues to be the leading cause of visual impairment for the elderly in developed countries. It is a complex, multifactorial, progressive disease with diverse molecular pathways regulating its pathogenesis. One of t ...
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Journal ArticleJCI Insight · September 6, 2018
Advanced age-related macular degeneration (AMD), the leading cause of blindness among people over 50 years of age, is characterized by atrophic neurodegeneration or pathologic angiogenesis. Early AMD is characterized by extracellular cholesterol-rich depos ...
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Journal ArticleBiochim Biophys Acta Mol Basis Dis · May 2018
The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, initially discovered for its role in regulating xenobiotic metabolism. There is extensive evidence supporting a multi-faceted role for AhR, modulating physiological pathways im ...
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Journal ArticleExpert Opin Drug Discov · April 2018
The impact of vision debilitating diseases is a global public health concern, which will continue until effective preventative and management protocols are developed. Two retinal diseases responsible for the majority of vision loss in the working age adult ...
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Journal ArticleExp Eye Res · September 2017
The mouse is one of the most commonly used mammalian systems to study human diseases. In particular it has been an invaluable tool to model a multitude of ocular pathologies affecting the posterior pole. The aim of this study was to create a comprehensive ...
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Journal ArticleEBioMedicine · August 2017
Diabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Severa ...
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Journal ArticleJ Biomol Screen · December 2016
Collectively, retinal diseases, including age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy, result in severe vision impairment worldwide. The absence and/or limited availability of successful drug therapies for these blindin ...
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Journal ArticleAging (Albany NY) · September 8, 2016
Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is a nuclear receptor that regulates differentiation, inflammation, lipid metabolism, extracellular matrix remodeling, and angiogenesis in multiple tissues. These pathways are also central to the pat ...
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Journal ArticleAdv Exp Med Biol · 2016
Age-related macular degeneration (AMD) is the leading cause of legal blindness and visual impairment in individuals over 60 years of age in the Western World. A common morphological denominator in all forms of AMD is the accumulation of microglia within th ...
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Journal ArticleJ Pathol · January 2015
The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling ...
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Journal ArticleAdv Exp Med Biol · 2014
Age-related macular degeneration (AMD) is the most important cause of blindness and visual impairment among the elderly. Nuclear receptors represent one of the largest families of transcription factors, with 48 present in the human genome. They are critica ...
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Journal ArticleInvest Ophthalmol Vis Sci · November 13, 2013
PURPOSE: Neovascular remodeling (NVR), the progression of small capillaries into large-caliber arterioles with perivascular fibrosis, represents a major therapeutic challenge in neovascular age-related macular degeneration (AMD). Neovascular remodeling occ ...
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Journal ArticleProc Natl Acad Sci U S A · October 22, 2013
The aryl hydrocarbon receptor (AhR) is a nuclear receptor that regulates xenobiotic metabolism and detoxification. Herein, we report a previously undescribed role for the AhR signaling pathway as an essential defense mechanism in the pathogenesis of early ...
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Journal ArticleMol Endocrinol · February 2011
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Retinal pigment epithelial (RPE) cells play a vital role in retinal physiology by forming the outer blood-retina barrier and supporting photoreceptor function. Retinopathies including age-related macular degeneration (AMD) involve physiological and patholo ...
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Journal ArticleProg Retin Eye Res · March 2010
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During the past ten years, dramatic advances have been made in unraveling the biological bases of age-related macular degeneration (AMD), the most common cause of irreversible blindness in western populations. In that timeframe, two distinct lines of evide ...
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Journal ArticleOphthalmology · February 2010
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PURPOSE: To characterize reticular pseudodrusen, a potential risk factor for late age-related macular degeneration. DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifty-eight eyes of 33 patients with pseudodrusen (20 female). METHODS: Cons ...
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Journal ArticleAdv Exp Med Biol · 2010
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The pathophysiology of 'early' dry age-related macular degeneration (ARMD), characterized by the accumulation of lipid and protein-rich sub-retinal deposits remains largely unknown. Accumulation and dysregulated turnover of lipids as well as extracellular ...
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Journal ArticleExp Eye Res · November 2008
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We demonstrate histologically sub-retinal drusenoid debris in three aged human eyes, two of them affected by age-related maculopathy. By postmortem fundus examination, the lesions were drusen-like, i.e., they were pale spots apparently at the level of the ...
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Journal ArticleBiochim Biophys Acta · September 2007
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The phosphatase of regenerating liver-1, PRL-1, gene was detected in a screen for foveal cone photoreceptor-associated genes. It encodes a small protein tyrosine phosphatase that was previously immunolocalized to the photoreceptors in primate retina. Here ...
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Journal ArticleAngiogenesis · 2007
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During the past few years systematic investigation into the epidemiology, genetics, and pathophysiology of age-related macular degeneration (AMD) has provided important new insight into this leading cause of vision loss in older persons. These studies prov ...
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OtherBr J Ophthalmol · September 2006
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Various combinations of risk factors and mechanisms may explain the complexity observed in AMD patients ...
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Journal ArticleExp Eye Res · December 2005
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To address the potential for an outer segment (OS) contribution to the sub-retinal pigment epithelium (RPE) lesions of age-related maculopathy (ARM), we quantified esterified and unesterified cholesterol (EC, UC) with the sterol-specific fluorescent probe ...
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Journal ArticleBiochem Biophys Res Commun · November 11, 2005
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To examine the effects and potential implications for the expression of the two basic fibroblast growth factor (bFGF) receptors, FGFR-1 and FGFR-2, in retinal pigment epithelial (RPE) cells, bFGF-dependent changes in gene expression and RPE cell function w ...
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Journal ArticleProc Natl Acad Sci U S A · August 16, 2005
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Age-related macular degeneration (AMD) is a late-onset, multifactorial, neurodegenerative disease of the retina and the leading cause of irreversible vision loss in the elderly in the Western world. We describe here a murine model that combines three known ...
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Journal ArticleInvest Ophthalmol Vis Sci · July 2005
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PURPOSE: To isolate and characterize cholesteryl ester-containing, lipoprotein-like particles (LLPs) from normal aged human Bruch's membrane (BrM)/choroid (Ch). METHODS: From BrM/Ch of 20 eyes of 10 donors aged >60 years, LLPs were released by high-salt bu ...
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Journal ArticleBiochem Biophys Res Commun · October 29, 2004
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Choroidal neovascularization (CNV) is a debilitating complication of age-related macular degeneration and a leading cause of vision loss. Along with other angiogenic factors like vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-1 ...
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Journal ArticleAm J Pathol · February 2003
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Lipids accumulate in Bruch's membrane (BrM), a specialized vascular intima of the eye, and in extracellular lesions associated with aging and age-related maculopathy (ARM). We tested the hypothesis that ARM and atherosclerotic cardiovascular disease share ...
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Journal ArticleOphthalmology · December 2000
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PURPOSE: To clarify the pathogenesis of late-onset retinal degeneration (L-ORD), an autosomal dominant disorder characterized by thick deposits of lipid-rich material between the retinal pigment epithelium (RPE) and Bruch's membrane. STUDY DESIGN: Comparat ...
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Journal ArticleOphthalmology · February 2000
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PURPOSE: To determine relationships among Bruch's membrane ultrastructure, photoreceptor degeneration, and choriocapillaris atrophy with respect to zones of retinal pigment epithelium (RPE) degeneration and atrophy adjacent to the optic nerve head, as a fu ...
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Journal ArticleOphthalmology · 2000
Objective: The trial evaluated the effectiveness of the investigational antihistaminic and antiallergic compound Azelastine Eye Drops (AZE) in the treatment of allergic conjunctivitis using an allergen challenge model. Design: Randomized, double-blind, pla ...
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