Visual Cycle: Dependence of Retinol Production and Removal on Photoproduct Decay and Cell Morphology

Ala-Laurila, Petri; Kolesnikov, Alexander V.; Crouch, Rosalie K.; Tsina, Efthymia; Shukolyukov, S.A.; Govardovskii, V. I.; Koutalos, Yiannis; Wiggert, Barbara; Estevez, Maureen E.; Cornwall, M. Carter

doi:10.1085/jgp.200609557

Cited by 78 publications

(90 citation statements)

References 59 publications

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“…As previously observed in salamander photoreceptors (22,24), both IRBP and BSA can facilitate the removal of all-trans retinol. Virtually all of the retinol can be removed, in accordance with the bulk of it being free (28).…”

Section: Discussionsupporting

confidence: 70%

“…Here, we have taken advantage of two properties of frog rod photoreceptors to actually measure the amounts of all-trans retinol produced with quantitative biochemical and physiological methods. One, in contrast to larval salamander photoreceptors that contain two types of chromophore (based on vitamins A 1 and A 2 ) and in widely varying ratios (24), frog rods contain a single, vitamin A 1 -based chromophore. Two, the metabolic supply of NADPH is not limiting for the formation of all-trans retinol in the case of frog rods (23), allowing a simplified analysis and direct comparisons between biochemical and physiological data.…”

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confidence: 99%

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Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Blakeley

Cornwall

et al. 2007

Biochemistry

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Light detection by vertebrate rod photoreceptor outer segments results in the destruction of the visual pigment, rhodopsin, as its retinyl moiety is photoisomerized from 11-cis to all-trans. The regeneration of rhodopsin is necessary for vision and begins with the release of the all-trans retinal and its reduction to all-trans retinol. Retinol is then transported out of the rod outer segment for further processing. We used fluorescence imaging to monitor retinol fluorescence and quantify the kinetics of its formation and clearance after rhodopsin bleaching in the outer segments of living isolated frog (Rana pipiens) rod photoreceptors. We independently measured the release of all-trans retinal from bleached rhodopsin in frog rod outer segment membranes and the rate of all-trans retinol removal by the lipophilic carriers interphotoreceptor retinoid binding protein (IRBP) and serum albumin. We find that the kinetics of all-trans retinol formation in frog rod outer segments after rhodopsin bleaching are to a good first approximation determined by the kinetics of all-trans retinal release from the bleached pigment. For the physiological concentrations of carriers, the rate of retinol removal from the outer segment is determined by the IRBP concentration, while the effect of serum albumin is negligible. The results indicate the presence of a specific interaction between IRBP and rod outer segment, probably mediated by a receptor. The effect of different concentrations of IRBP on the rate of retinol removal shows no cooperativity and has an EC 50 of 40 μmol/L.The vertebrate cells responsible for vision are the rod and cone photoreceptors of the retina that convert incoming light to an electrical signal. This conversion takes place in the photoreceptor outer segments, which are full of membrane disks containing the visual pigment, and, in a physiologically important arrangement, are enveloped by the retinal pigment epithelium (RPE). The visual pigment is composed of a chromophore, 11-cis retinal, attached to an integral membrane protein, opsin. The detection of light begins with the absorption of incoming photons by the visual pigment. An absorbed photon isomerizes the chromophore † Supported by NIH/NEI grants EY14850 (YK), EY04939 (RKC) , NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript moiety from 11-cis to all-trans bringing about a conformational change that initiates a cascade of reactions culminating in membrane potential change. The recovery of the cell from light involves the deactivation of the intermediates activated by light, and the reestablishment of membrane potential (1,2). However, the isomerized chromophore, all-trans retinal, remains. For vision to be possible, it is essential that the visual pigment regenerate: that is, the alltrans retinal has to be removed, and fresh 11-cis retinal has to be provided to combine with opsin and reform the visual pigment. The reactions regenerating the pigment are known as the Visual Cycle (3-5).In the case of the rod photoreceptors, t...

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Section: Discussionsupporting

confidence: 70%

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Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Blakeley

Cornwall

et al. 2007

Biochemistry

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“…Fluorescence-After mouse or other vertebrate rod and cone photoreceptors are exposed to light, there is an increase in the outer segment fluorescence that has been attributed to the formation of all-trans-retinol (28,31,33). Fig.…”

Section: Rdh8-dependent Light-induced Increases In Rod Cellmentioning

confidence: 99%

Reduction of All-trans-retinal in Vertebrate Rod Photoreceptors Requires the Combined Action of RDH8 and RDH12

Chen

Thompson

Koutalos

2012

Journal of Biological Chemistry

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Background: Retinoid dehydrogenases/reductases (RDHs) reduce retinal in rod photoreceptors. Results: In single rod cells, RDH8 reduces retinal generated in outer segments; RDH12 reduces retinal that escapes to inner segments. Conclusion: By detoxifying stray retinal, RDH12 acts as a barrier against intracellular aldehyde diffusion. Significance: This protective role is consistent with the severe pathology resulting from RDH12 mutations in human disease.

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“…There is some evidence suggesting that visual cycle reactions also proceed faster in cones than in rods (11,12). The rate of conversion of all-trans-retinal to all-trans-retinol is 10 -40 times faster in isolated salamander cones than that in rods (11).…”

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RPE65 from Cone-dominant Chicken Is a More Efficient Isomerohydrolase Compared with That from Rod-dominant Species

Moiseyev

Takahashi

Chen

et al. 2008

Journal of Biological Chemistry

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Cones recover their photosensitivity faster than rods after bleaching. It has been suggested that a higher rate regeneration of 11-cis-retinal, the chromophore for visual pigments, is required for cones to continuously function under bright light conditions. RPE65 is the isomerohydrolase catalyzing a key step in regeneration of 11-cis-retinal. The present study investigated whether RPE65 in a cone-dominant species is more efficient in its enzymatic activity than that from roddominant species. In vitro isomerohydrolase activity assay showed that isomerohydrolase activity in the chicken retinal pigment epithelium (RPE) was 11.7-fold higher than in the bovine RPE, after normalization by RPE65 protein levels. Similar to that of human and bovine, the isomerohydrolase activity in chicken RPE was blocked by two specific inhibitors of lecithin retinal acyltransferase, indicating that chicken RPE65 also uses all-trans-retinyl ester as the direct substrate. To exclude the possibility that the higher isomerohydrolase activity in the chicken RPE could arise from another unknown isomerohydrolase, we expressed chicken and human RPE65 using the adenovirus system in a stable cell line expressing lecithin retinal acyltransferase. Under the same conditions, isomerohydrolase activity of recombinant chicken RPE65 was 7.7-fold higher than that of recombinant human RPE65, after normalization by RPE65 levels. This study demonstrates that RPE65 from the cone-dominant chicken RPE possesses significantly higher specific retinol isomerohydrolase activity, when compared with RPE65 from rod-dominant species, consistent with the faster regeneration rates of visual pigments in cone-dominant retinas.Visual pigments of rods and cones consist of protein opsins and the chromophore, 11-cis-retinal covalently bound to opsins via a Schiff base (1). Upon light absorption, the 11-cis-retinal is photoisomerized to all-trans-retinal, which subsequently activates opsin and triggers the phototransduction cascade (1, 2). The 11-cis-retinal chromophore regenerates through a series of reactions of the retinoid visual cycle (3, 4). The visual cycle has been intensively studied in rod-dominant species such as bovine and mouse. The twocell (photoreceptor and RPE) 2 system of 11-cis-retinal recycling has been proposed for the visual cycle. After reduction of all-trans-retinal by retinol dehydrogenase, the generated all-trans-retinol is transported from the photoreceptor to the RPE and esterified to all-trans-retinyl esters by lecithin retinol acyltransferase (LRAT). The resulting all-trans-retinyl ester can either be stored in the RPE or directly converted to 11-cis-retinol by the isomerohydrolase, which was recently identified as the microsomal protein RPE65 (5-7). RPE65 has been shown to be an essential enzyme in the retinoid visual cycle for 11-cis-retinal regeneration (8). After oxidation of 11-cis-retinol by retinol dehydrogenase-5, the generated 11-cis-retinal is transported back to the photoreceptors to regenerate the visual pigments.It is known that cone...

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Visual Cycle: Dependence of Retinol Production and Removal on Photoproduct Decay and Cell Morphology

Cited by 78 publications

References 59 publications

Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Interphotoreceptor Retinoid-Binding Protein Is the Physiologically Relevant Carrier That Removes Retinol from Rod Photoreceptor Outer Segments

Reduction of All-trans-retinal in Vertebrate Rod Photoreceptors Requires the Combined Action of RDH8 and RDH12

RPE65 from Cone-dominant Chicken Is a More Efficient Isomerohydrolase Compared with That from Rod-dominant Species

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