Role of photoreceptor-specific retinol dehydrogenase in the retinoid cycle in vivo.
The retinoid cycle is a recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. Photoreceptor-specific retinol dehydrogenase (prRDH) catalyzes reduction of all-trans-retinal to all-trans-retinol and is thought to be a key enzyme in the retinoid cycle. We disrupted mouse prRDH (human gene symbol RDH8) gene expression by targeted recombination and generated a homozygous prRDH knock-out (prRDH-/-) mouse. Histological analysis and electron microscopy of retinas from 6- to 8-week-old prRDH-/- mice revealed no structural differences of the photoreceptors or inner retina. For brief light exposure, absence of prRDH did not affect the rate of 11-cis-retinal regeneration or the decay of Meta II, the activated form of rhodopsin. Absence of prRDH, however, caused significant accumulation of all-trans-retinal following exposure to bright lights and delayed recovery of rod function as measured by electroretinograms and single cell recordings. Retention of all-trans-retinal resulted in slight overproduction of A2E, a condensation product of all-trans-retinal and phosphatidylethanolamine. We conclude that prRDH is an enzyme that catalyzes reduction of all-trans-retinal in the rod outer segment, most noticeably at higher light intensities and prolonged illumination, but is not an essential enzyme of the retinoid cycle.
Maeda
Akiko
A
Department of Ophthalmology, University of Washington, Seattle, Washington 98195-6485, USA.
Maeda
Tadao
T
Imanishi
Yoshikazu
Y
Kuksa
Vladimir
V
Alekseev
Andrei
A
Bronson
J Darin
JD
Zhang
Houbin
H
Zhu
Li
L
Sun
Wenyu
W
Saperstein
David A
DA
Rieke
Fred
F
Baehr
Wolfgang
W
Palczewski
Krzysztof
K
D000429:Alcohol Oxidoreductases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015139:Blotting, Southern; D002384:Catalysis; D002460:Cell Line; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004596:Electroretinography; D005123:Eye / Q000378:metabolism; D005822:Genetic Vectors; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007313:Insecta; D007700:Kinetics; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D008957:Models, Genetic; D009154:Mutation; D010714:Phosphatidylethanolamines / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011995:Recombination, Genetic; D012160:Retina / Q000378:metabolism*; D012172:Retinaldehyde / Q000737:chemistry; D012176:Retinoids / Q000737:chemistry / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D019076:Transgenes; D014801:Vitamin A / Q000378:metabolism
D018076:DNA, Complementary; D010714:Phosphatidylethanolamines; D012333:RNA, Messenger; D012176:Retinoids; D014801:Vitamin A; C483858:phosphatidylethanolamine; D012243:Rhodopsin; D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase; D012172:Retinaldehyde