Delayed dark adaptation in 11-cis-retinol dehydrogenase-deficient mice: a role of RDH11 in visual processes in vivo.
The oxidation of 11-cis-retinol to 11-cis-retinal in the retinal pigment epithelium (RPE) represents the final step in a metabolic cycle that culminates in visual pigment regeneration. Retinol dehydrogenase 5 (RDH5) is responsible for a majority of the 11-cis-RDH activity in the RPE, but the formation of 11-cis-retinal in rdh5-/- mice suggests another enzyme(s) is present. We have previously shown that RDH11 is also highly expressed in RPE cells and has dual specificity for both cis- and trans-retinoid substrates. To investigate the role of RDH11 in the retinoid cycle, we generated rdh11-/- and rdh5-/-rdh11-/- mice and examined their electrophysiological responses to various intensities of illumination and during dark adaptation. Retinoid profiles of darkadapted rdh11-/- mice did not show significant differences compared with wild-type mice, whereas an accumulation of cis-esters was detected in rdh5-/- and rdh5-/-rdh11-/- mice. Following light stimulation, 73% more cis-retinyl esters were stored in rdh5-/-rdh11-/- mice compared with rdh5-/- mice. Single-flash ERGs of rdh11-/- showed normal responses under dark- and light-adapted conditions, but exhibited delayed dark adaptation following high bleaching levels. Double knockout mice also had normal ERG responses in dark- and light-adapted conditions, but had a further delay in dark adaptation relative to either rdh11-/- or rdh5-/- mice. Taken together, these results suggest that RDH11 has a measurable role in regenerating the visual pigment by complementing RDH5 as an 11-cis-RDH in RPE cells, and indicate that an additional unidentified enzyme(s) oxidizes 11-cis-retinol or that an alternative pathway contributes to the retinoid cycle.
Kim
Tom S
TS
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Maeda
Akiko
A
Maeda
Tadao
T
Heinlein
Cynthia
C
Kedishvili
Natalia
N
Palczewski
Krzysztof
K
Nelson
Peter S
PS
D000221:Adaptation, Ocular / Q000502:physiology*; D000429:Alcohol Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003624:Darkness; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010857:Pigment Epithelium of Eye / Q000502:physiology*; D016133:Polymerase Chain Reaction; D012160:Retina / Q000201:enzymology*
D017931:DNA Primers; D010446:Peptide Fragments; D000429:Alcohol Oxidoreductases; C022520:retinol dehydrogenase