RPE65

About RPE65

RPE65 on chromosome 1p31.3 encodes an isomerohydrolase in the retinal pigment epithelium that converts all trans retinyl esters into 11 cis retinol, a key step in the visual cycle that regenerates the chromophore needed by rod and cone photoreceptors. Without it, photoreceptors cannot respond properly to light. Variants on both copies of RPE65 cause a form of Leber congenital amaurosis and early onset retinal dystrophy, characterized by severe visual impairment and night blindness from infancy or early childhood with later loss of photoreceptors. RPE65 disease achieved a landmark in medicine in 2017 when voretigene neparvovec, an AAV vector delivering a working copy of the gene under the retina, became the first gene therapy for an inherited disease approved by the US Food and Drug Administration. It requires that patients still have enough viable retinal cells.