Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor
Berry, Michael H.
Gaub, Benjamin M.
Kim, Yang J.
Kramer, Richard H.
Isacoff, Ehud Y.
- Journal Article
Rights / licenseCreative Commons Attribution 4.0 International
Retinitis pigmentosa results in blindness due to degeneration of photoreceptors, but spares other retinal cells, leading to the hope that expression of light-activated signaling proteins in the surviving cells could restore vision. We used a retinal G protein-coupled receptor, mGluR2, which we chemically engineered to respond to light. In retinal ganglion cells (RGCs) of blind rd1 mice, photoswitch-charged mGluR2 (“SNAG-mGluR2”) evoked robust OFF responses to light, but not in wild-type retinas, revealing selectivity for RGCs that have lost photoreceptor input. SNAG-mGluR2 enabled animals to discriminate parallel from perpendicular lines and parallel lines at varying spacing. Simultaneous viral delivery of the inhibitory SNAG-mGluR2 and excitatory light-activated ionotropic glutamate receptor LiGluR yielded a distribution of expression ratios, restoration of ON, OFF and ON-OFF light responses and improved visual acuity. Thus, SNAG-mGluR2 restores patterned vision and combinatorial light response diversity provides a new logic for enhanced-acuity retinal prosthetics. Show more
Journal / seriesNature Communications
Pages / Article No.
PublisherNature Publishing Group
SubjectMolecular neuroscience; Protein design; Retina
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Is referenced by: https://doi.org/10.1038/s41467-018-03585-2
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