During past year, we investigated of using ERG recording as a tool to understand the changes in visual signal pathway and processing mechanisms in the cone-only retina of Nrl-ko mouse. Nrl is a transcription factor that controls the fate of photoreceptor progenitor cells. Lack of Nrl expression in Nrl-ko mouse retina leads to the conversion of rod photoreceptors to cone photoreceptors. Nrl-ko mouse has been proposed to serve as a model for human macular dieseases. Using ERG recording methods, we found that Compared with wild-type animal, Nrl-ko mice exhibited larger b-wave amplitudes and a higher sensitivity for UV flash ERG. On the other hand, Nrl-ko mice had smaller b-wave amplitudes and a lower sensitivity for ERG responses elicited by green light. ERG responses to green flashes had a faster kinetics with shortening in both latency and peak implicit time than those evoked by UV flashes. UV flicker ERG responses had a frequency-response turning curve that lied in between WT scotopic and photopic response curves, whereas green flicker responses followed closely to WT photopic response curve. Based on these results, we hypothesized that there are two subtypes of cone photoreceptors are present in the Nrl-ko animals. Majority of them expresses high levels of S-opsin and also communicates with rod-bipolar cells in the retina. This pathway mediates large, highly sensitive, and slow UV flash ERG responses. M-opsin is preferentially expressed in a small subset of cone photoreceptors, and these photoreceptors likely only connect with cone-bipolar cells. This hypothesis is supported by immunocytochemical studies which revealed selective connection between PKC-positive rod-bipolar cells and photoreceptors expressing high-level of S-opsin. Our ERG results are also consistent with the observation that Nrl-ko mice exhibited a slight lower spatial sensitivity than wild-type controls. In conclusion, our study indicated that non-invasive ERG recordings could provide valuable sights into the signal processing mechanisms in the mouse retina.

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