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 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. Age-related macular degeneration (AMD) is a leading cause of blindness and is characterised by the accumulation of lipid deposits, called drusen. Here, the authors show that mice lacking chloride intracellular channel 4 in retinal pigment epithelium have defective lipid processing in the eye and pathological features mirroring human AMD, including drusen formation.

Automated summary

In this study, researchers observed that mice lacking chloride intracellular channel 4 in retinal pigment epithelium exhibited a full spectrum of functional and pathological features of dry AMD, including drusen formation. Multidisciplinary longitudinal studies revealed a mechanistic link between RPE cell-autonomous aberrant lipid metabolism and transport and drusen formation.