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 H. Yang, Maxwell P. Lee, Armaan F. Akbar, Tudor C. Badea, Ziqi Guo, Afnan Nuruzzaman, Kuo‐Shun Hsu, Joshua L. Dunaief, Ching‐Hwa Sung
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.