It is not known why APOE4, which acts detrimentally in the brain, seems to offer protection in the retina—and why the opposite is true for APOE2. In the retina, APOE is expressed locally by the RPE and Müller glia and is an abundant constituent of drusen in both AMD and non-AMD patients [39]. This evidence concerns the gene APOE and age-related macular degeneration.