Active Cholesterol Efflux in the Retina and Retinal Pigment Epithelium

The importance of cholesterol as a structural component of photoreceptors and the association between impaired cholesterol homeostasis and age-related macular degeneration (AMD) prompted in the last years a deep investigation of its metabolism in the retina. Here, we focus on the export of cholesterol from intracellular membranes to extracellular acceptors, an active mechanism mediated by the ATP-binding cassette transporters A1 and G1 (ABCA1 and G1) also known as "active cholesterol efflux." Expression of genes involved in this pathway was shown for most retinal cells, while functional in vitro assays focused on the retinal pigment epithelium (RPE) due to availability of cell models. Cell-specific knockout (KO) mice were generated in the past years, and their characterization unveils an important role of the ABCA1/G1 pathway in RPE, rods, and retinal inflammatory cells. The actual involvement of cholesterol efflux in the pathogenesis of AMD still needs to be demonstrated and will help in establishing the scientific rationale for targeting the ABCA1/G1 pathway in retinal diseases.