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Sergey Girman, Shaomei Wang; Earliest manifestation of MERTK mutation: Abnormal ERG recovery after brief exposure to moderate light in very young RCS rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):733.
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MERTK mutation in RCS rats affects the RPE cells, primarily their ability to phagocytise the photoreceptor outer segments; that leads to a progressive photoreceptor loss and visual impairment. If the mutation affects the RPE visual cycle, and, through that, the vision, is less clear. We studied whether the recovery of ERG responses in RCS rats after exposure to light in physiological range deviate from norm before the photoreceptor loss.
We recorded ERG responses in 21-23 days old dark-adapted pigmented RCS rats to trains of test light flashes of low intensity; the inter-flash intervals progressively increased from 0.8 up to 30 s. We made sure that each test flash, even that following previous one after a minimal interval, evoked responses of the same amplitude (around 40 uv), thus not inducing any noticeable adaptation effect. Then we introduced, at the beginning of the test flash series, the conditioning exposure to the light which duration (0.1-3 s) and brightness (5-30 cd/m2) were varied in different experiments. We measured ERG responses to the test flashes following the conditioning one. The series duration was adjusted so that at the end of each series the responses restored to the initial dark-adapted amplitude. The series was repeated several (5-15) times, mean and standard errors of amplitudes were obtained. This procedure allowed us to evaluate the time course of ERG recovery (driven by recycling 11-cis-retinal in the RPE) after the conditioning flash. Control recordings were obtained from age-matched Long Evans rats.
In RCS rat the conditioning flash induced significantly stronger, comparing with normal rat, suppression of ERG responses and this effect was more prolonged. The time profile of ERG recovery in RCS noticeably differed from an exponential asymptotic rise to dark-adapted level, displaying, most often, three distinct phases: an initial fast (but slower than normal) increase of response amplitudes, then responses decrease, and finally they rise almost linearly to dark-adapted value. Amplitude and timing of these phases depended on the parameters of the conditioning flash.
Time course of ERG recovery after exposure to moderate light in very young RCS rat differs significantly from that in normal rat suggesting that RCS rat vision is affected by malfunction of RPE retinoid cycle.
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