Localization and function of proteins involved in visual chromophore production in the vertebrate retina.A, vision is initiated by the absorption of light (hν, yellow highlight) by visual pigments localized in the photoreceptor outer segments (central region of the panel; rod outer segment on the left, cone outer segments in the middle and right). These outer segments are connected to the photoreceptor inner segments and cell bodies shown in the bottom portion of the panel (unlabeled). Protein-mediated pathways required for 11-cis-retinal synthesis and the regeneration of the visual pigment molecules reside in the RPE (upper panel) and Müller cells [bottom panel; note: only the Müller cell microvilli (wavy gray structures) are shown]. Enzymes and retinoid-binding proteins are shown in pink and dark blue boxes, respectively. Note the presence of light-dependent and light-independent pathways in both RPE and Müller cells. Dashed lines indicate retinoid diffusion/transport pathways of unclear function. Abbreviations are as follows: 11cRAL, 11-cis-retinal; 11cRDH, 11-cis-RDH; 11cRE, 11-cis-retinyl esters; 11cROL, 11-cis-retinol; atRAL, all-trans-retinal; atRDH, all-trans-RDH; atRE, all-trans-retinyl esters; atROL, all-trans-retinol; CRALBP, cellular retinaldehyde-binding protein; IRBP, interphotoreceptor retinoid-binding protein; RGR, retinal G-protein-coupled receptor; RDH, retinol dehydrogenase. Question marks indicate steps where a physiologically relevant enzyme has yet to be identified. B–C, single-cell RNA sequencing analysis of visual-cycle-associated proteins in the peripheral (B) and central (C) regions of the human retina. The area of each circle indicates the expression level of the given gene (shown on the horizontal axis) in each cell type (vertical axis). Data are taken from reference (18).