Figure 1. The visual cycle in the vertebrate retina. The classical visual cycle is a chain of biochemical reactions that are catalyzed by retinoid dehydrogenase/reductase (RDH) in photoreceptors or the retinal pigment epithelia (RPE) and are responsible for regenerating visual pigment following light exposure [28]. The visual process is initiated by the photoisomerization of 11-cis-retinal (11cRAL) to all-trans-retinal (atRAL). First, 11cRAL diffuses from the RPE to photoreceptor-rod outer segments (OS; rod outer segments, ROS; and cone outer segments, COS) and is coupled to opsin to generate rhodopsin (Rh; reaction a). Then, in the photoreceptor outer segments, the absorption of light by rhodopsin causes isomerization of the chromophore from the 11-cis form to the all-trans form (reaction b). The atRAL is reduced to all-trans-retinol (atROL) in the reaction catalyzed by an nicotinamide-adenine dinucleotide phosphate (NADPH)-dependent all-trans-retinal-specific dehydrogenase (all-trans-RDH, RDH8, RDH12; reaction c) [8,22]. Next, atROL diffuses to the RPE, where it is esterified to all-trans-retinyl-ester (atRE) in a reaction catalyzed by lecithin: retinol acyltransferase (LRAT; reaction d). The isomerization of atRE to 11cROL is catalyzed by RPE-specific 65 kDa protein (RPE65; reaction e), which is the key step in the retinoid visual cycle [29-31]. 11cROL is then oxidized by 11-cis-RDH (RDH5, RDH11) to 11cRAL to complete the retinoid cycle (reaction f). IPM, interphotoreceptor matrix; IRBP, inter-photoreceptor retinol binding protein.