Retinoid requirements for recovery of sensitivity after visual-pigment bleaching in isolated photoreceptors.

Abstract

After visual-pigment bleaching, single isolated rod photoreceptors of Ambystoma tigrinum recover their sensitivity to light when supplied with 11-cis-retinal from liposomes or with li-cis-retinal bound to interphotoreceptor retinoid-binding protein. Bleached rods do not recover sensitivity, or do so only very slowly, after exposure to 11-cis-retinol. The latter retinoid is "toxic" in that rods actually lose sensitivity in its presence. In contrast, bleached isolated cone cells recover sensitivity when either retinoid is supplied. It is suggested that the major pathway for rhodopsin regeneration during dark adaptation in the intact eye is transport of ll-cis-retinal from the pigment epithelium to the retina. The results also suggest that there may be separate pathways for visual-pigment regeneration in rods and cones during dark adaptation.Regeneration of visual pigment during dark adaptation or during maintained illumination requires retinoid isomerization from trans to cis form and conversion from alcohol to aldehyde before retinoid can be bound to opsin to reconstitute active pigment (1). The pigment epithelium (PE) has long been known to be involved in regeneration (2), implying a "visual cycle" that involves shuttling of retinoid from retina to PE and back again during cycles of light and dark. During light adaptation, there is indeed a progressive loss of retinoid from the retina, and an increase in the retinoid content of the PE. During darkness, the retinoid flow is reversed (3). Fulton and Rando (4) have presented strong evidence for localization of the retinoid-isomerizing system in PE rather than retina, but it remains uncertain which cells are involved in effecting the alcohol-to-aldehyde change that must take place during the visual cycle.We now report a difference in the use of retinol and retinal by rod and cone cells, and a "toxic" effect of retinol on rod cell function. We suggest that 11-cis-retinal is the major form of retinoid transported from PE to retina. Alternatively, ifthe alcohol form is transported it must be converted to the aldehyde in a cell type other than the rod photoreceptor (which may be cones, or possibly Muller cells).Pepperberg et al. (5) showed that the ordinarily permanent desensitization due to bleaching in isolated retina could be reversed by treatment with 11-cis-retinal. In their work, retinal was applied in ethanolic solution. Subsequently, it was shown (6) that liposomes could also be used to deliver retinoid. Our studies on isolated photoreceptors have employed both liposomes and interphotoreceptor retinoidbinding protein (IRBP). IRBP is a protein found at high concentration in the interphotoreceptor matrix, where its unique location and retinoid-binding properties (7,8) make it likely that it is involved in retinoid movement between retina and PE. In support of this, we demonstrate here the transfer of retinoid between IRBP and photoreceptor cells. MATERIALS AND METHODSIsolated photoreceptor cells from dark-adapted, larval tiger salamanders (Ambystoma tigrin...

Identification of the 11- cis- specific retinyl-ester synthase in retinal Müller cells as multifunctional O- acyltransferase (MFAT)

“…Cones, but not rods, can use 11-cis-ROL as a chromophore precursor to regenerate bleached opsin pigments (10,12,13). The isomerase in the noncanonical pathway is dihydroceramide desaturase (DES1) (11).…”

Parallel visual cycles in the zebrafish retina

“…Moreover, it had been shown in the 1980s that in the retina of the cone-dominant chicken the major source of retinylesters are 11-cis REs localized inside the neural retina, whereas rod-dominant species, such as frogs and cows show a pre-dominance of all-trans REs in the RPE (Bridges and Alvarez, 1987;Rodriguez and Tsin, 1989). Bleached salamander rod outer segments are only capable of recovering their visual sensitivity upon administration of exogenous 11-cis RAL, but not ROL, whereas cones were able to utilize both retinoid sources (Jones et al, 1989).…”

“…Knocking-down either cralbp paralog did not result in complete absence of 11-cis RAL, as cone photoreceptors are capable of utilizing the 2 nd source of recycled visual pigment (from the RPE or Müller cells). It has been shown that cone photoreceptors possess a 11-cis ROL dehydrogenase activity, capable of oxidizing 11-cis ROL into 11-cis RAL (Jones et al, 1989;Mata et al, 2002), and are able to regenerate visual pigment from 11-cis ROL or 11-cis RAL (Jones et al, 1989).…”

“…Cone but not rod photoreceptors seem capable of oxidizing 11-cis ROL to 11-cis RAL (Jones et al, 1989). Such an 11-cis retinol dehydrogenase (RDH) activity preferring NADP+ as a cofactor had then been isolated in chicken and ground squirrel microsomes, and suggested to be implicated in this cone-specific oxidation step (Mata et al, 2002;Mata et al, 2005).…”

Evolution and the origin of the visual retinoid cycle in vertebrates

“…In the cone-dominant retina, the oxidation of 11-cis-ROL to 11-cis-RAL is NADP dependent and takes places in cones (Mata et al 2002), whereas in rod-dominant eyes, this oxidation reaction is NAD dependent. In an early study using isolated rods and cones from salamander, it was shown that 11-cis-ROL added to the medium could confer light sensitivity to photobleached cones, but not to rods ( Jones et al 1989), suggesting that cones contain RDH(s) that catalyses oxidation of 11-cis-ROL to 11-cis-RAL. Haeseleer et al (2002) showed that RDH12 expressed in the photoreceptors could be involved in the production of 11-cis-RAL from 11-cis-ROL during regeneration of the cone visual pigments.…”