Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration

Significance Recessive Stargardt macular degeneration (STGD1) and a subset of cone–rod dystrophies are caused by mutations in the Abca4 gene. The ABCA4 protein is a flippase in photoreceptor cells that helps eliminate retinaldehyde, a toxic photoproduct of vision. Here we found that ABCA4 is additionally present in the retinal pigment epithelium (RPE) of mice at approximately 1% of its abundance in the neural retina. Genetically modified mice that express ABCA4 in RPE but not in photoreceptor cells showed partial rescue of both the lipofuscin accumulation and photoreceptor degeneration observed in Abca4 −/− mice and in STGD1 patients. These observations suggest that ABCA4 in the RPE prevents photoreceptor degeneration in Abca4 −/− mice and possibly in STGD1 patients.