A proposed role for all-trans retinal in regulation of rhodopsin regeneration in human rods

Abstract

In order to account for the multi-phasic dynamics of photopigment regeneration in human rods, we developed a new model of the retinoid cycle. We first examined the relative roles of the classical and channeling mechanisms of metarhodopsin decay in establishing these dynamics. We showed that neither of these mechanisms alone, nor a linear combination of the two, can adequately account for the dynamics of rhodopsin regeneration at all bleach levels. Our new model adds novel inhibitory interactions in the cycle of regeneration of rhodopsin that are consistent with the 3D structure of rhodopsin. Our analyses show that the dynamics of human rod photopigment regeneration can be accounted for by end-product regulation of the channeling mechanism where all-trans retinal (tral) inhibits the binding of 11-cis retinal to the opsin.tral complex.

Human Blue Cone Opsin Regeneration Involves Secondary Retinal Binding with Analog Specificity

“…The channeling hypothesis proposes that the retinal entrance/exit is controlled by receptor conformational changes that open/close the gates to the channel (34,37). Accordingly, upon SB hydrolysis, ATR may be initially trapped into the binding pocket, blocking the entrance of a fresh 11CR molecule (38). In our model, the secondary retinal uptake into regenerated cone opsins may function as an 11CR buffer, which may compensate for the fast decay of the photoactivated conformation of cone opsins.…”

Light and ocular immunity

“…Light deprivation of a specific wavelength (500-510 nm) prevented the formation of regulatory T cells and abolished ACAID following inoculation of antigen into the anterior chamber [8,57]. Zhou et al [64 && ] performed an interesting experiment in which they showed that the generation of regulatory T cells by TGF-b in vivo is dependent on the presence of retinoic acid, an oxidized form of vitamin A -the latter is a major component of the visual pathway in photoreceptors [65,66].…”

Rescue and repair during photoreceptor cell renewal mediated by docosahexaenoic acid-derived neuroprotectin D1

“…When rhodopsin interacts with a photon, 11-cis -retinal is isomerized to all-trans -retinal. The regeneration of 11-cis-retinal from all-trans -retinal takes place between the photoreceptor outer segment and the RPE ( 24 ). All-trans -retinol is esterifi ed with a fatty acid to be isomerized to 11-cis -retinol and hydrolyzed from the ester bond in RPE cells.…”