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S Nusinowitz, LT Nguyen, DB Farber, M Danciger; Electrophysiological Evidence for Slower Photoreceptor Recovery in Albino Mice with the MET450 Variant in the Rpe65 Gene . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3758.
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Purpose: In previous quantitative genetic studies with c2J and BALB/cByJ albino mice, the MET450 variant in the c2J Rpe65 protein (BALB/c has LEU450) was found to cosegregate with a substantial portion of the light damage protection exhibited by the c2J strain (Danciger, et al. Mamm. Genome 11: 422-27, 2000). Wenzel et al. (J. Neurosci. 21:53-58, 2001) showed that mice with MET450 had slower regeneration of rhodopsin and correlated this with the protective effect. We reasoned that c2J mice with MET450 should recover vision from intense light exposure more slowly than the LEU450 BALB/c mice, and tested this hypothesis electrophysiologically. Methods: Full-field ERGs were recorded from c2J and BALB/c albino mice and C57BL/6J pigmented controls. Rod-mediated ERGs were recorded to blue flashes with sufficient intensity to saturate the ERG a-wave. The leading edge of the a-wave was fitted with a rod model to provide estimates for td, the time before response onset, S, a sensitivity parameter, and Rmp3, the maximum saturated photovoltage reflecting activation steps. The kinetics of recovery from bright flash stimulation was studied using a two-flash paradigm. Recovery was inferred from the amplitude of the a-wave to a probe flash that was preceded at varying times by a bright conditioning flash. The normalized a-wave response function was fitted with an exponential relation to derive Tc, the critical delay and the recovery time constant. Results: The parameters, td and Rmp3 were found not to be significantly different among the three strains of mice. In contrast, the parameter, S, was 0.27 log unit higher (P<0.0001) for the c2J albino mice compared to pigmented controls, and the BALB/c mean value was 0.42 log unit higher (P<0.0001). The double flash experiments indicated that albino mice are slower to recover from bright flashes compared to pigmented mice and that among the albinos, c2J mice are slower to recover than BALB/c mice. For the conditions of these experiments, Tc was 1.02, 5.28, and 7.34 sec for the C57, BALB/c, and c2J mice, respectively, and the corresponding time constants were 35.5, 60.9, and 67.0 seconds. Conclusion: ERG recordings show that c2J albino mice with the MET450 variant of RPE65 have a lower gain and a slower recovery from bright flash stimulation than do BALB/c albinos. These results contribute to the explanation of why c2J photoreceptors are protected from the stress of prolonged light exposure.
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