Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. Dry AMD has unclear etiology and no treatment. Lipid-rich drusen are the hallmark of dry AMD. An AMD mouse model and insights into drusenogenesis are keys to better understanding of this disease. Chloride int...

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Autores principales: Chuang, Jen-Zen, Yang, Nan, Nakajima, Nobuyuki, Otsu, Wataru, Fu, Cheng, Yang, Howard Hua, Lee, Maxwell Ping, Akbar, Armaan Fazal, Badea, Tudor Constantin, Guo, Ziqi, Nuruzzaman, Afnan, Hsu, Kuo-Shun, Dunaief, Joshua L., Sung, Ching-Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766482/
https://www.ncbi.nlm.nih.gov/pubmed/35042858
http://dx.doi.org/10.1038/s41467-021-27935-9
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author Chuang, Jen-Zen
Yang, Nan
Nakajima, Nobuyuki
Otsu, Wataru
Fu, Cheng
Yang, Howard Hua
Lee, Maxwell Ping
Akbar, Armaan Fazal
Badea, Tudor Constantin
Guo, Ziqi
Nuruzzaman, Afnan
Hsu, Kuo-Shun
Dunaief, Joshua L.
Sung, Ching-Hwa
author_facet Chuang, Jen-Zen
Yang, Nan
Nakajima, Nobuyuki
Otsu, Wataru
Fu, Cheng
Yang, Howard Hua
Lee, Maxwell Ping
Akbar, Armaan Fazal
Badea, Tudor Constantin
Guo, Ziqi
Nuruzzaman, Afnan
Hsu, Kuo-Shun
Dunaief, Joshua L.
Sung, Ching-Hwa
author_sort Chuang, Jen-Zen
collection PubMed
description Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. Dry AMD has unclear etiology and no treatment. Lipid-rich drusen are the hallmark of dry AMD. An AMD mouse model and insights into drusenogenesis are keys to better understanding of this disease. Chloride intracellular channel 4 (CLIC4) is a pleomorphic protein regulating diverse biological functions. Here we show that retinal pigment epithelium (RPE)-specific Clic4 knockout mice exhibit a full spectrum of functional and pathological hallmarks of dry AMD. Multidisciplinary longitudinal studies of disease progression in these mice support a mechanistic model that links RPE cell-autonomous aberrant lipid metabolism and transport to drusen formation.
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spelling pubmed-87664822022-02-04 Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration Chuang, Jen-Zen Yang, Nan Nakajima, Nobuyuki Otsu, Wataru Fu, Cheng Yang, Howard Hua Lee, Maxwell Ping Akbar, Armaan Fazal Badea, Tudor Constantin Guo, Ziqi Nuruzzaman, Afnan Hsu, Kuo-Shun Dunaief, Joshua L. Sung, Ching-Hwa Nat Commun Article Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. Dry AMD has unclear etiology and no treatment. Lipid-rich drusen are the hallmark of dry AMD. An AMD mouse model and insights into drusenogenesis are keys to better understanding of this disease. Chloride intracellular channel 4 (CLIC4) is a pleomorphic protein regulating diverse biological functions. Here we show that retinal pigment epithelium (RPE)-specific Clic4 knockout mice exhibit a full spectrum of functional and pathological hallmarks of dry AMD. Multidisciplinary longitudinal studies of disease progression in these mice support a mechanistic model that links RPE cell-autonomous aberrant lipid metabolism and transport to drusen formation. Nature Publishing Group UK 2022-01-18 /pmc/articles/PMC8766482/ /pubmed/35042858 http://dx.doi.org/10.1038/s41467-021-27935-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Chuang, Jen-Zen
Yang, Nan
Nakajima, Nobuyuki
Otsu, Wataru
Fu, Cheng
Yang, Howard Hua
Lee, Maxwell Ping
Akbar, Armaan Fazal
Badea, Tudor Constantin
Guo, Ziqi
Nuruzzaman, Afnan
Hsu, Kuo-Shun
Dunaief, Joshua L.
Sung, Ching-Hwa
Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration
title Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration
title_full Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration
title_fullStr Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration
title_full_unstemmed Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration
title_short Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration
title_sort retinal pigment epithelium-specific clic4 mutant is a mouse model of dry age-related macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766482/
https://www.ncbi.nlm.nih.gov/pubmed/35042858
http://dx.doi.org/10.1038/s41467-021-27935-9
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