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Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE

AMD is the leading cause of blindness in developed countries. The dry form of AMD, also known as atrophic AMD, is characterized by the death of RPE and photoreceptors. Currently, there are no treatments for this form of the disease due in part to our incomplete understanding of the mechanism causing...

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Detalles Bibliográficos
Autores principales: Fisher, Cody R., Ferrington, Deborah A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989860/
https://www.ncbi.nlm.nih.gov/pubmed/30025108
http://dx.doi.org/10.1167/iovs.18-24289
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author Fisher, Cody R.
Ferrington, Deborah A.
author_facet Fisher, Cody R.
Ferrington, Deborah A.
author_sort Fisher, Cody R.
collection PubMed
description AMD is the leading cause of blindness in developed countries. The dry form of AMD, also known as atrophic AMD, is characterized by the death of RPE and photoreceptors. Currently, there are no treatments for this form of the disease due in part to our incomplete understanding of the mechanism causing AMD. Strong experimental evidence from studies of human donors with AMD supports the emerging hypothesis that defects in RPE mitochondria drive AMD pathology. These studies, using different experimental methods, have shown disrupted RPE mitochondrial architecture and decreased mitochondrial number and mass, altered content of multiple mitochondrial proteins, increased mitochondrial DNA damage that correlates with disease severity, and defects in bioenergetics for primary RPE cultures from AMD donors. Herein, we discuss a model of metabolic uncoupling that alters bioenergetics in the diseased retina and drives AMD pathology. These data provide the rationale for targeting the mitochondria in the RPE as the most efficacious intervention strategy if administered early, before vision loss and cell death.
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spelling pubmed-59898602018-06-07 Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE Fisher, Cody R. Ferrington, Deborah A. Invest Ophthalmol Vis Sci Special Issue AMD is the leading cause of blindness in developed countries. The dry form of AMD, also known as atrophic AMD, is characterized by the death of RPE and photoreceptors. Currently, there are no treatments for this form of the disease due in part to our incomplete understanding of the mechanism causing AMD. Strong experimental evidence from studies of human donors with AMD supports the emerging hypothesis that defects in RPE mitochondria drive AMD pathology. These studies, using different experimental methods, have shown disrupted RPE mitochondrial architecture and decreased mitochondrial number and mass, altered content of multiple mitochondrial proteins, increased mitochondrial DNA damage that correlates with disease severity, and defects in bioenergetics for primary RPE cultures from AMD donors. Herein, we discuss a model of metabolic uncoupling that alters bioenergetics in the diseased retina and drives AMD pathology. These data provide the rationale for targeting the mitochondria in the RPE as the most efficacious intervention strategy if administered early, before vision loss and cell death. The Association for Research in Vision and Ophthalmology 2018-06 /pmc/articles/PMC5989860/ /pubmed/30025108 http://dx.doi.org/10.1167/iovs.18-24289 Text en Copyright 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Special Issue
Fisher, Cody R.
Ferrington, Deborah A.
Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE
title Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE
title_full Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE
title_fullStr Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE
title_full_unstemmed Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE
title_short Perspective on AMD Pathobiology: A Bioenergetic Crisis in the RPE
title_sort perspective on amd pathobiology: a bioenergetic crisis in the rpe
topic Special Issue
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989860/
https://www.ncbi.nlm.nih.gov/pubmed/30025108
http://dx.doi.org/10.1167/iovs.18-24289
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