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CM Donmoyer, K Lai, J Kong, G Duester, A Molotkov, WS Blaner, P Gouras; Impairment of Dark Adaptation in ADH4-/-RDH5-/- Double Knockout Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3681.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine dark adaptation of ADH4-/-RDH5-/- double knockout mice by recording a- and b-wave amplitudes. Alcohol dehydrogenase class IV (ADH4) and cis retinol dehydrogenase type 5 (RDH5) are enzymes located in the retinal pigment epithelium. Both enzymes are able to catalyze steps needed in the visual cycle. Methods: Electroretinograms (ERGs) were performed on female age-matched, overnight dark-adapted wild type (WT; n=3), ADH4-/- (n=3), RDH5-/- (n=3), and ADH4-/-RDH5-/- (DKO; n=5) mice under anesthesia. After the dark-adapted a- and b-waves were measured, mice were light-adapted for 5 min (350 cd/m2) and the recordings were continued in the dark (flash frequency = 0.05 Hz). Body temperature was maintained using a variable heating stage. Results: Maximum b-wave amplitudes in all groups were comparable during the initial dark-adapted period, indicating the absence of retinal degeneration. In the WT, RDH5-/-, and DKO groups, b-wave amplitudes were 44%, 26% and 20% of maximum amplitudes at 5 min after the bleach, respectively. At 20 min post bleach, b-wave amplitudes were 71%, 37% and 31%. Values for ADH4-/- mice were midway between WT and DKO (32% and 43% at 5 and 20 min post bleach). There were no significant differences in the a-wave amplitudes between groups. Conclusion: The b-wave amplitudes of RDH5-/- and DKO mice were at least 50% reduced compared to WT mice at equivalent timepoints during recovery, indicating that the time course of recovery was slower in both mutant groups. ADH4-/- mice also displayed a delay in recovery relative to WT. These data suggest that these genetic knockouts give rise to an impairment of the visual cycle during dark adaptation. However, the enzymes may have redundant roles in the visual cycle. We are presently examining the biochemistry involved in these alterations.
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