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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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Detalles Bibliográficos
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:
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
Descripción
Sumario: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.