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Pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice
Age-related macular degeneration (AMD) is the major cause of blindness in the elderly in developed countries and its prevalence is increasing with the aging population. AMD initially affects the retinal pigment epithelium (RPE) and gradually leads to secondary photoreceptor degeneration. Recent stud...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176989/ https://www.ncbi.nlm.nih.gov/pubmed/29925537 http://dx.doi.org/10.1242/dmm.032698 |
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author | Zhang, Meng Chu, Yi Mowery, Joseph Konkel, Brandon Galli, Susana Theos, Alexander C. Golestaneh, Nady |
author_facet | Zhang, Meng Chu, Yi Mowery, Joseph Konkel, Brandon Galli, Susana Theos, Alexander C. Golestaneh, Nady |
author_sort | Zhang, Meng |
collection | PubMed |
description | Age-related macular degeneration (AMD) is the major cause of blindness in the elderly in developed countries and its prevalence is increasing with the aging population. AMD initially affects the retinal pigment epithelium (RPE) and gradually leads to secondary photoreceptor degeneration. Recent studies have associated mitochondrial damage with AMD, and we have observed mitochondrial and autophagic dysfunction and repressed peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α; also known as Ppargc1a) in native RPE from AMD donor eyes and their respective induced pluripotent stem cell-derived RPE. To further investigate the effect of PGC-1α repression, we have established a mouse model by feeding Pgc-1α(+/−) mice with a high-fat diet (HFD) and investigated RPE and retinal health. We show that when mice expressing lower levels of Pgc-1α are exposed to HFD, they present AMD-like abnormalities in RPE and retinal morphology and function. These abnormalities include basal laminar deposits, thickening of Bruch's membrane with drusen marker-containing deposits, RPE and photoreceptor degeneration, decreased mitochondrial activity, increased levels of reactive oxygen species, decreased autophagy dynamics/flux, and increased inflammatory response in the RPE and retina. Our study shows that Pgc-1α is important in outer retina biology and that Pgc-1α(+/−) mice fed with HFD provide a promising model to study AMD, opening doors for novel treatment strategies. |
format | Online Article Text |
id | pubmed-6176989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-61769892018-10-16 Pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice Zhang, Meng Chu, Yi Mowery, Joseph Konkel, Brandon Galli, Susana Theos, Alexander C. Golestaneh, Nady Dis Model Mech Research Article Age-related macular degeneration (AMD) is the major cause of blindness in the elderly in developed countries and its prevalence is increasing with the aging population. AMD initially affects the retinal pigment epithelium (RPE) and gradually leads to secondary photoreceptor degeneration. Recent studies have associated mitochondrial damage with AMD, and we have observed mitochondrial and autophagic dysfunction and repressed peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α; also known as Ppargc1a) in native RPE from AMD donor eyes and their respective induced pluripotent stem cell-derived RPE. To further investigate the effect of PGC-1α repression, we have established a mouse model by feeding Pgc-1α(+/−) mice with a high-fat diet (HFD) and investigated RPE and retinal health. We show that when mice expressing lower levels of Pgc-1α are exposed to HFD, they present AMD-like abnormalities in RPE and retinal morphology and function. These abnormalities include basal laminar deposits, thickening of Bruch's membrane with drusen marker-containing deposits, RPE and photoreceptor degeneration, decreased mitochondrial activity, increased levels of reactive oxygen species, decreased autophagy dynamics/flux, and increased inflammatory response in the RPE and retina. Our study shows that Pgc-1α is important in outer retina biology and that Pgc-1α(+/−) mice fed with HFD provide a promising model to study AMD, opening doors for novel treatment strategies. The Company of Biologists Ltd 2018-09-01 2018-08-16 /pmc/articles/PMC6176989/ /pubmed/29925537 http://dx.doi.org/10.1242/dmm.032698 Text en © 2018. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Zhang, Meng Chu, Yi Mowery, Joseph Konkel, Brandon Galli, Susana Theos, Alexander C. Golestaneh, Nady Pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice |
title | Pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice |
title_full | Pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice |
title_fullStr | Pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice |
title_full_unstemmed | Pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice |
title_short | Pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice |
title_sort | pgc-1α repression and high-fat diet induce age-related macular degeneration-like phenotypes in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176989/ https://www.ncbi.nlm.nih.gov/pubmed/29925537 http://dx.doi.org/10.1242/dmm.032698 |
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