Retinol dehydrogenases (RDHs) in the visual cycle

Abstract

The isomerization of 11-cis retinal to all-trans retinal in photoreceptors is the first step in vision. For photoreceptors to function in constant light, the all-trans retinal must be converted back to 11-cis retinal via the enzymatic steps of the visual cycle. Within this cycle, all-trans retinal is reduced to all-trans retinol in photoreceptors and transported to the retinal pigment epithelium (RPE). In the RPE, all-trans retinol is converted to 11-cis retinol, and in the final enzymatic step, 11-cis retinol is oxidized to 11-cis retinal. The first and last steps of the classical visual cycle are reduction and oxidation reactions, respectively, that utilize retinol dehydrogenase (RDH) enzymes. The visual cycle RDHs have been extensively studied, but because multiple RDHs are capable of catalyzing each step, the exact RDHs responsible for each reaction remain unknown. Within rods, RDH8 is largely responsible for the reduction of all-trans retinal with possible assistance from RDH12. retSDR1 is thought to reduce all-trans retinal in cones. In the RPE, the oxidation of 11-cis retinol is carried out by RDH5 with possible help from RDH11 and RDH10. Here, we review the characteristics of each RDH in vitro and the findings from knockout models that suggest the roles for each in the visual cycle.