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Yichao Li, Jerome Roger, Rivka Rachel, Anand Swaroop, Haohua Qian; Effects of Nrl knockout on visual signal in mouse retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2676. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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. The purpose of this study is to understand the changes in visual signal pathway and processing mechanisms in the cone-only retina of Nrl-ko mouse.
Adult wild type (C57BL/6J) and Nrl-ko animals (2-4 month old) were used in this study. ERG responses were recorded with E2 system (Diagnosys LLC) and light stimuli were generated by UV (365nm) and green (514nm) LED. Expression patterns of M-opsin in the retina were examined by immunohistochemistry. The OptoMotry system (CerebralMechanics Inc.) was used to measure spatial sensitivity of mice by their opto-kinetic tracking (OKT) responses.
Compared with WT animal, Nrl-ko mice exhibited larger b-wave amplitudes and a higher sensitivity for UV flash ERG (Rmax=550 ± 35 µV and 273 ± 25 µV, σ=1.3×10^3 and 7.2×10^3 photons/µm^2 for Nrl-ko (n=6) and WT (n=4), respectively). On the other hand, Nrl-ko mice had smaller b-wave amplitudes and a lower sensitivity for ERG responses elicited by green light (Rmax=185 ± 20 µV and 275 ± 30 µV, σ=1.0×10^5 and 2.3×10^4 photons/µm^2 for Nrl-ko (n=6) and WT (n=4), respectively). ERG responses to green flashes had a faster kinetics with shortening in both latency and peak implicit time than those evoked by UV flashes (n=6). 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. Spatial sensitivities measured by opto-kinetic tracking responses to visible light stimuli were 0.354 ± 0.001 c/deg for Nrl-ko (n=4) and 0.384 ± 0.002 c/deg for WT (n=5). Immunohistochemistry revealed M-opsin was preferentially expressed in a small subset of cone photoreceptors in Nrl-ko retina.
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. Spatial sensitivity determined by visible-wavelength light is largely mediated by this pathway.
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