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V. Busskamp, D. Balya, B. Roska; Expression of a Red-Light Sensitive Chloride Pump in Photoreceptors Changes the Spectral Tuning of Mouse Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4876. doi: https://doi.org/.
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The goal of this study was to test whether the red light-sensitive chloride pump NpHR from the archaea Natronomonas pharaonis could be used to modulate photoreceptor activity. A potential use of this pump 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 NpHR in photoreceptors of C57BL/6 mice using AAV2/7 vector mediated gene transfer. NpHR was driven from the rhodopsin promoter. The retina was stimulated at different wavelengths and the spiking activity of ganglion cells was measured using multielectrode arrays.
AAV2/7 mediated gene transfer led to the expression of NpHR in most photoreceptors (90%) in the infected area. The spectral tuning curve of AAV infected retinas showed significantly higher light sensitivity at longer wavelengths compared to control uninfected retinas.
Our results indicate that light-sensitive chloride pump can modulate photoreceptor activity. This approach might be useful to confer light sensitivity to rd retinas at early stages of rd when photosensitivity is lost but the first retinal synapse is still intact.
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