Isomerization and Oxidation of Vitamin A in Cone-Dominant Retinas

Mata, Nathan L.; Radu, Roxana A.; Clemmons, Richard S.; Travis, Gabriel H.

doi:10.1016/s0896-6273(02)00912-1

Cited by 328 publications

(179 citation statements)

References 59 publications

(67 reference statements)

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“…It was also reported that chicken eyecups contain lower levels of all-trans-retinyl ester but higher levels of 11-cis-retinyl esters than that in mammalian eyes (12,26). The higher isomerohydrolase activity in the chicken RPE could also be responsible for the lower level of all-trans-retinyl esters in the chicken RPE, because all-trans-retinyl esters are more efficiently converted to 11-cis-retinol, which is consequently esterified to 11-cis-retinyl esters for storage (12,26).…”

Section: Discussionmentioning

confidence: 95%

“…The chicken retina contains ϳ60% cones, whereas human and bovine retinas have ϳ5% cones (12). Physiological measurements have shown that cones have much faster photoresponse kinetics than rods (9,10).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that a unique characteristic of the isomerase in cone-dominant species is that it directly utilizes all-trans-retinol as the substrate and converts it directly to 11-cis-retinol without formation of the intermediate retinyl esters (12,26). On the contrary, the rod-dominant retinol isomerase requires the formation of retinyl esters that are a direct substrate for the isomerohydrolase (16,24).…”

Section: Discussionmentioning

confidence: 99%

“…The higher isomerohydrolase activity in the chicken RPE could also be responsible for the lower level of all-trans-retinyl esters in the chicken RPE, because all-trans-retinyl esters are more efficiently converted to 11-cis-retinol, which is consequently esterified to 11-cis-retinyl esters for storage (12,26). It has been shown that Rpe65 Ϫ/Ϫ mice lack any 11-cis-retinoids in the retina or RPE (8), suggesting that RPE65 is the only isomerase in the RPE, at least in mammals.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

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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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