biostudies-literatureChuang JZU.S. Department of Health & Human Services | NIH | National Eye InstituteNEI NIH HHSResearch to Prevent BlindnessAlcon FoundationNIGMS NIH HHS374https://www.ebi.ac.uk/biostudies/studies/S-EPMC8766482biostudies-literatureUnknown13(1)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 communicationsRetinal pigment epithelium-specific CLIC4 mutant is a mouse model of dry age-related macular degeneration.PMC8766482R01 EY029428P30 EY001583EY015240R01 EY032966EY 032966P41 GM103310EY 029428R01 EY028916R01 EY015240Sung CHBadea TCGuo ZYang NDunaief JLNakajima NYang HHAkbar AFFu CNuruzzaman AChuang JZOtsu WLee MPHsu KSfalseRetinal 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 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.2022-01-01T00:00:00Z2022 Jan2026-07-14T15:01:33.342Z2025-04-19T15:44:09.284ZS-EPMC87664823504285810.1038/s41467-021-27935-9