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J. Duebel, V. Busskamp, D. Balya, B. Roska; Light-Sensitive Neuromodulators enable wavelength-specific control of Mouse Photoreceptor Activity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):668.
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The goal of this study was to test whether the red-light-sensitive chloride pump NpHR and the blue-light sensitive cation channel ChR2 could be used to modulate photoreceptor activity. A potential use of this approach is to restore vision at early stages of retinal degeneration when photoreceptor function is lost but the photoreceptor-to-bipolar synapse may still be intact.
Whole-cell patch-clamp recordings were performed of photoreceptors in C57BL/6-mice expressing NpHR alone or together with ChR2. Ganglion cell activity of retinas expressing NpHR in their photoreceptors was measured in cell-attached and whole-cell configuration. For retinal stimulation monochromatic light at different wavelengths (390-690nm) was used.
Red-light stimulation of NpHR-expressing photoreceptors induced rapid outward currents of up to 70 pA resulting in hyperpolarization of the membrane potential. Illumination at different wavelengths led to different current amplitudes matching the action spectrum of NpHR with an excitation maximum near 570 nm. Ganglion cells of retinas expressing NpHR in their photoreceptors showed significantly higher light sensitivity at longer wavelengths (500-600nm) compared to unifected control retinas. NpHR-ChR2-coexpressing photoreceptors responded to red light with an outward current and to blue light with an inward current, indicating hyperpolarization and depolarization, respectively.
Our results show that light-sensitive neuromodulators are functional in photoreceptors. Coexpression of NpHR and ChR2 enables the bidirectional modulation of the photoreceptor membrane potential. This approach might be useful to confer light sensitivity to blind mice at early stages of retinal degeneration.
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