Isolated Retinas Synthesize Visual Pigments from Retinol Congeners Delivered by Liposomes

Uoshikami, S; Nöll, Gottfried N.

doi:10.1126/science.307275

Cited by 46 publications

(12 citation statements)

References 13 publications

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“…After bleaching of the isolated retina, 11-cis-retinol has been found to promote recovery of rod sensitivity or visualpigment regeneration in the amphibian retina but not in the mammalian retina; 11-cis-retinal is effective in both cases (6,16,24). This result can be reconciled with the present data only if the amphibian retina is able to convert 11-cis-retinol to retinal within cells other than the rod photoreceptors.…”

Section: Discussionsupporting

confidence: 53%

“…A possible small resensitization was found after 150 min, but this amounted to a decrease in threshold of at most 0.2 log unit, which translates according to the data of Liebovic et al (11) into a pigment regeneration rate of 0.04% min-. This is 10 times lower than the maximal regeneration rates found with 11-cis-retinol in the intact retina (6,16). Full visual-pigment regeneration at this rate would take several days.…”

Section: Discussionmentioning

confidence: 75%

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

Jones

Crouch

Wiggert

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

204

155

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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...

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 75%

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

Jones

Crouch

Wiggert

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

204

155

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“…Another reductase role for cRDH was first proposed by Lion et al (12). Most models of the visual cycle since then have emphasized the oxidation reaction of cRDH instead, because no experiment to regenerate rhodopsin with 11-cis-retinol in excised mammalian retina has succeeded (45)(46)(47). On the other hand, cone pigments in excised retina can be regenerated with 11-cis-retinol (48).…”

Section: Figmentioning

confidence: 99%

Interaction of 11-cis-Retinol Dehydrogenase with the Chromophore of Retinal G Protein-coupled Receptor Opsin

Chen

Lee

Fong

2001

Journal of Biological Chemistry

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Vertebrate opsins in both photoreceptors and the retinal pigment epithelium (RPE) have fundamental roles in the visual process. The visual pigments in photoreceptors are bound to 11-cis-retinal and are responsible for the initiation of visual excitation. Retinochrome-like opsins in the RPE are bound to all-trans-retinal and play an important role in chromophore metabolism. The retinal G protein-coupled receptor (RGR) of the RPE and Mü ller cells is an abundant opsin that generates 11-cisretinal by stereospecific photoisomerization of its bound all-trans-retinal chromophore. We have analyzed a 32-kDa protein (p32) that co-purifies with bovine RGR from RPE microsomes. The co-purified p32 was identified by mass spectrometric analysis as 11-cis-retinol dehydrogenase (cRDH), and enzymatic assays have confirmed the isolation of an active cRDH. The co-purified cRDH showed marked substrate preference to 11-cisretinal and preferred NADH rather than NADPH as the cofactor in reduction reactions. cRDH did not react with endogenous all-trans-retinal bound to RGR but reacted specifically with 11-cis-retinal that was generated by photoisomerization after irradiation of RGR. The reduction of 11-cis-retinal to 11-cis-retinol by cRDH enhanced the net photoisomerization of all-trans-retinal bound to RGR. These results indicate that cRDH is involved in the processing of 11-cis-retinal after irradiation of RGR opsin and suggest that cRDH has a novel role in the visual cycle.The continual synthesis of rhodopsin by recombination of its apoprotein with the chromophore, 11-cis-retinal, is an essential process that maintains visual excitation (1, 2). It has long been known that formation of 11-cis-retinal for regeneration of rhodopsin is dependent on retinoid metabolic reactions in the retinal pigment epithelium (RPE), 1 where the majority of enzymes of the visual cycle are located (reviewed in Ref. 3). In the current model of the visual cycle, all-trans-retinal from bleached rhodopsin is reduced to all-trans-retinol by an alltrans-retinol-specific dehydrogenase (tRDH) located in photoreceptor outer segments (4 -6). The all-trans-retinol is then delivered to the RPE, where it is converted by the lecithin: retinol acyltransferase to all-trans-retinyl ester (7,8). A key step in the visual cycle is performed by an isomerohydrolase that catalyzes the formation of 11-cis-retinol from all-transretinyl ester (9 -10). Alternatively, the isomerization of alltrans-retinol to 11-cis-retinol is achieved via an intermediate with an anhydro-like carbocation structure (11). An 11-cisretinol-specific dehydrogenase (cRDH) is able to oxidize 11-cisretinol to 11-cis-retinal (12-14), which is transferred to the outer segments of photoreceptors for recombination with opsin to form rhodopsin. Under light-adapted conditions, the rate of synthesis of 11-cis-retinal must be sufficient for regeneration of steady-state levels of visual pigments (15, 16).Besides isomerohydrolase, another type of isomerase in the RPE may include the retinochrome-like visual pigment ...

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“…This calculation does not take into account the small amount of pigment regeneration (< 5%) which has been reported to occur in isolated retina in the absence of extrinsic chromophore (Azuma, Azuma & Sickel, 1977;Cocozza & Ostroy, 1987 (Yoshikami & Noll, 1978). The method for the preparation of the liposomes was given in a previous publication (Jin et al 1993).…”

mentioning

confidence: 99%

Bleached pigment activates transduction in isolated rods of the salamander retina.

Cornwall

Fain

1994

The Journal of Physiology

194

200

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1. We have used suction electrode recording together with rapid steps into Li' solution and 0 5 mM IBMX solution to estimate the rates of the guanylyl phosphodiesterase (PDE) and guanylyl cyclase in isolated rods of the salamander, Ambystoma tigrinum. 2. We show that both the PDE and cyclase velocities are accelerated by steady background light. The steady velocities of both enzymes appear to be saturating functions of background intensity. 3. Bleaching also accelerates both the PDE and cyclase. This effect is maintained long after the bleaching stimulus is removed (up to 2 h) and is reversed only if the photopigment is regenerated with exogenous chromophore. 4. The estimated steady-state PDE and cyclase velocities appear to be linear functions of the amount of pigment bleached, as if each bleached pigment molecule activated the transduction cascade with the same probability and gain. 5. The effectiveness of bleached pigment in activating transduction is only 10-6 to times that of activated rhodopsin (Rh*), but this is sufficient after large bleaches to produce an 'equivalent background' excitation of the rod, which is probably responsible, at least in part, for bleaching desensitization.When the eye is exposed to light bright enough to bleach a significant fraction of the visual pigment, the sensitivity of the visual system is greatly depressed and recovers slowly. This phenomenon, known as dark adaptation or bleaching adaptation, is still poorly understood. Since the recovery of sensitivity has a time course which is approximately the same as the regeneration of visual pigment (Rushton, 1965), it is reasonable to suppose that the loss of pigment is somehow responsible for the loss of sensitivity. However, it has long been realized that the decrease in sensitivity is much greater than would be expected from the decrease in the probablility of light absorption by the photopigment (Campbell & Rushton, 1955). The visual system appears to produce a bleaching signal that elevates threshold much more than simple loss of pigment would predict.To investigate the nature of this bleaching signal, we have recorded from isolated rods of the salamander, Ambystoma tigrinum. Earlier experiments have shown that the bleaching of pigment in these photoreceptors produces a loss of sensitivity which, like that in the visual system as a whole, is considerably greater than expected from the decrease in pigment concentration (Cornwall, Fein & MacNichol, 1990). Furthermore, the light responses of bleached rods at steady state have many of the characteristics of those of rods in the presence of background light: sensitivity is decreased, circulating current is reduced, and the decay time of the response to brief flashes is accelerated. These observations suggest that bleaching may desensitize the rods by producing an 'equivalent background' excitation, as first suggested from psychophysical experiments by Stiles & Crawford (1932).Furthermore, the similarity of responses in the presence of background light and after bleaches suggests t...

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Isolated Retinas Synthesize Visual Pigments from Retinol Congeners Delivered by Liposomes

Cited by 46 publications

References 13 publications

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

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

Interaction of 11-cis-Retinol Dehydrogenase with the Chromophore of Retinal G Protein-coupled Receptor Opsin

Bleached pigment activates transduction in isolated rods of the salamander retina.

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