RPE65 has an additional function as the lutein to meso -zeaxanthin isomerase in the vertebrate eye

Significance Carotenoids are plant-derived pigment molecules that cannot be synthesized de novo by higher organisms. These physiologically relevant compounds function as potent antioxidants and light screening compounds, and their supplementation has been shown to ameliorate the progression of such diseases as age-related macular degeneration. Hundreds of carotenoids are present in the plant world, but the primate macula contains only three: lutein, zeaxanthin, and meso -zeaxanthin. The presence of meso -zeaxanthin in the foveal region of primates is an unexplained phenomenon, given its lack of dietary sources. We show that RPE65 is responsible for the conversion of lutein to meso -zeaxanthin in vertebrates, a unique role for RPE65 in carotenoid metabolism beyond its well-known retinoid isomerohydrolase function in the vertebrate visual cycle.