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V. Busskamp, J. Duebel, D. Balya, J. Hall, B. Roska; Expression of Light-Sensitive Neuromodulators in Photoreceptors Changes the Spectral Tuning of Mouse Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3893.
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The aim of this study was to test whether light-sensitive neuromodulatorscould be used to modulate photoreceptor activity. A potential use of this approach is at early stages of retinal degeneration (rd) when photoreceptor function is lost but the photoreceptor-to-bipolar synapse may still be intact.
We expressed the red-light-sensitive chloride pump NpHR alone and together with the blue-light-sensitive cation channel ChR2 in photoreceptors of C57BL/6. Gene transfer was done by using Adeno-Associated-Viruses (AAV). For photoreceptor-specific expression, the human rhodopsin promoter, the human red opsin promoter and the mouse cone arrestin3 promoter were used. The expression levels of the neuromodulators were analyzed by imaging techniques. The retina was stimulated at different wavelengths and the spiking activity of ganglion cells was measured using multielectrode arrays.
AAV-mediated gene transfer led to the expression of NpHR and/or ChR2 in many photoreceptors in the infected area. The used AAVs differed in their infection pattern regarding rod and cone photoreceptors. The spectral tuning curve of NpHR-AAV-infected retinas showed significantly higher light sensitivity at longer wavelengths compared to control uninfected retinas.
Our results indicate that light-sensitive neuromodulators can modulate photoreceptor activity. Coexpression of NpHR and ChR2 enables the possibility to adjust the photoreceptor resting potential in a push-pull manner. This approach might be useful to confer light sensitivity to rd retinas at early stages of rd.
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