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

Jen Zen Chuang; Nan Yang; Nobuyuki Nakajima; Wataru Otsu; Cheng Fu; Howard Hua Yang; Maxwell Ping Lee; Armaan Fazal Akbar; Tudor Constantin Badea; Ziqi Guo; Afnan Nuruzzaman; Kuo Shun Hsu; Joshua L. Dunaief; Ching Hwa Sung

doi:10.1038/s41467-021-27935-9

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

Jen Zen Chuang, Nan Yang, Nobuyuki Nakajima, Wataru Otsu, Cheng Fu, Howard Hua Yang, Maxwell Ping Lee, Armaan Fazal Akbar, Tudor Constantin Badea, Ziqi Guo, Afnan Nuruzzaman, Kuo Shun Hsu, Joshua L. Dunaief, Ching Hwa Sung

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13 Scopus citations

Abstract

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.

Original language	English (US)
Article number	374
Journal	Nature communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-27935-9
State	Published - Dec 2022
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Chuang, J. Z., Yang, N., Nakajima, N., Otsu, W., Fu, C., Yang, H. H., Lee, M. P., Akbar, A. F., Badea, T. C., Guo, Z., Nuruzzaman, A., Hsu, K. S., Dunaief, J. L., & Sung, C. H. (2022). Retinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration. Nature communications, 13(1), Article 374. https://doi.org/10.1038/s41467-021-27935-9

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

abstract = "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.",

author = "Chuang, {Jen Zen} and Nan Yang and Nobuyuki Nakajima and Wataru Otsu and Cheng Fu and Yang, {Howard Hua} and Lee, {Maxwell Ping} and Akbar, {Armaan Fazal} and Badea, {Tudor Constantin} and Ziqi Guo and Afnan Nuruzzaman and Hsu, {Kuo Shun} and Dunaief, {Joshua L.} and Sung, {Ching Hwa}",

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doi = "10.1038/s41467-021-27935-9",

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AU - Chuang, Jen Zen

AU - Yang, Nan

AU - Nakajima, Nobuyuki

AU - Otsu, Wataru

AU - Fu, Cheng

AU - Yang, Howard Hua

AU - Lee, Maxwell Ping

AU - Akbar, Armaan Fazal

AU - Badea, Tudor Constantin

AU - Guo, Ziqi

AU - Nuruzzaman, Afnan

AU - Hsu, Kuo Shun

AU - Dunaief, Joshua L.

AU - Sung, Ching Hwa

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

Abstract

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