Peropsin modulates transit of vitamin A from retina to retinal pigment epithelium

Abstract

Edited by Velia M. FowlerPeropsin is a non-visual opsin in both vertebrate and invertebrate species. In mammals, peropsin is present in the apical microvilli of retinal pigment epithelial (RPE) cells. These structures interdigitate with the outer segments of rod and cone photoreceptor cells. RPE cells play critical roles in the maintenance of photoreceptors, including the recycling of visual chromophore for the opsin visual pigments. Here, we sought to identify the function of peropsin in the mouse eye. To this end, we generated mice with a null mutation in the peropsin gene (Rrh). These mice exhibited normal retinal histology, normal morphology of outer segments and RPE cells, and no evidence of photoreceptor degeneration. Biochemically, Rrh ؊/؊ mice had ϳ2-fold higher vitamin A (all-trans-retinol (all-trans-ROL)) in the neural retina following a photobleach and 5-fold lower retinyl esters in the RPE. This phenotype was similar to those reported in mice that lack interphotoreceptor retinoid-binding protein (IRBP) or cellular retinol-binding protein, suggesting that peropsin plays a role in the movement of all-trans-ROL from photoreceptors to the RPE. We compared the phenotypes in mice lacking both peropsin and IRBP with those of mice lacking peropsin or IRBP alone and found that the retinoid phenotype was similarly severe in each of these knock-out mice. We conclude that peropsin controls all-trans-ROL movement from the retina to the RPE or may regulate all-trans-ROL storage within the RPE. We propose that peropsin affects light-dependent regulation of all-trans-ROL uptake from photoreceptors into RPE cells through an as yet undefined mechanism.

Transcriptome Analyses of lncRNAs in A2E-Stressed Retinal Epithelial Cells Unveil Advanced Links between Metabolic Impairments Related to Oxidative Stress and Retinitis Pigmentosa

“…RPE expresses factors required for lipoprotein intake, cholesterol and lipoprotein synthesis and secretion, as well as reverse cholesterol transport (RCT) [94]. Phagocytosis and degradation of the POSs are the principal lipid source for the RPE [95], as well as processing and recycling back to the photoreceptors of vitamin A and of DHA [96,97]. Moreover, excess cholesterol is loaded on HDLs by ABC transporters and, then, removed, or it is also secreted in VLDL-like lipoproteins basolaterally into Bruch's membrane where it forms drusen [98].…”

Interphotoreceptor Retinoid-Binding Protein (IRBP) in Retinal Health and Disease

“…It mediates extracellular diffusion of retinoids during the operation of the retinoid cycle, transporting alltrans-retinol and 11-cis-retinal between the photoreceptors and the RPE (Gonzalez-Fernandez, 2003). A recent study suggested that IRBP may not be the only vehicle and peropsin may also transport all-trans-retinol from the neural retina to RPE (Cook et al, 2017). Human organic anion transporting polypeptide 1A2 (OATP1A2) has been recently found to be expressed at the apical membrane of RPE, where it facilitates the cellular uptake of all-trans-retinol into the RPE cells (Chan et al, 2015).…”

Evolutionary Constraint on Visual and Nonvisual Mammalian Opsins

“…Unlike RGR, RRH has retained the DRY sequence within the ionic lock switch as well as other GPCR features necessary for structure, G protein signaling, and retinal binding ( Figure 2c ). While no functions for RRH have been established in mammals beyond photoisomerization and retinal transport, it is interesting that arachnid RRH is in an active, potentially signaling state in the dark and is suppressed by light ( Cook et al, 2017 ; Nagata et al, 2018 ). Not only do these results suggest that RRH may have G protein signaling functions, but that the functions of RRH are conserved in all mammals, regardless of their lighting environment although decreased sequence constraint in subterrestrial/nocturnal mammals demonstrate a spectrum of biological selection.…”