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 et al. · Nat Commun · 2022

basic_science · Level V

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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.

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