RPE65

RPE65 is a gene that plays a critical role in the visual cycle, which is essential for the conversion of light into electrical signals by the retina in the eye. The RPE65 gene encodes the retinal pigment epithelium-specific 65 kDa protein. This protein is located in the retinal pigment epithelium (RPE), a layer of cells that nourishes the retinal cells and is vital for their function. The RPE65 protein is involved in the production of 11-cis-retinal, a molecule necessary for the regeneration of the visual pigment rhodopsin, which is critical for vision in low-light conditions.

Function[edit | edit source]

The primary function of the RPE65 protein is in the visual cycle. It acts as an isomerohydrolase, converting all-trans-retinyl esters to 11-cis-retinol, which is then oxidized to 11-cis-retinal. This molecule combines with opsin to form rhodopsin, the light-sensitive pigment in the photoreceptor cells of the retina. Without the activity of RPE65, the visual cycle stalls, leading to a buildup of all-trans-retinyl esters and a deficiency of 11-cis-retinal, resulting in impaired vision or blindness.

Genetic and Clinical Aspects[edit | edit source]

Mutations in the RPE65 gene are associated with several inherited retinal dystrophies, including Leber congenital amaurosis (LCA), an early-onset severe retinal degeneration, and certain forms of retinitis pigmentosa (RP), characterized by progressive peripheral vision loss and night blindness. These conditions are part of a group of genetic disorders known as inherited retinal dystrophies (IRDs), which lead to progressive loss of vision and can be severe.

Treatment and Research[edit | edit source]

The discovery of the RPE65 gene's role in the visual cycle has led to significant advancements in gene therapy for treating inherited retinal dystrophies. One notable example is voretigene neparvovec (Luxturna), the first gene therapy approved by the FDA for treating RPE65 mutation-associated inherited retinal dystrophies. This therapy involves delivering a normal copy of the RPE65 gene directly into the retina, aiming to restore the production of the RPE65 protein and, consequently, the visual cycle.