Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor

Michael H. Berry, Amy Holt, Joshua Levitz, Johannes Broichhagen, Benjamin M. Gaub, Meike Visel, Cherise Stanley, Krishan Aghi, Yang Joon Kim, Kevin Cao, Richard H. Kramer, Dirk Trauner, John Flannery and Ehud Y. Isacoff ()
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Michael H. Berry: University of California
Amy Holt: University of California
Joshua Levitz: University of California
Johannes Broichhagen: Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13
Benjamin M. Gaub: University of California
Meike Visel: University of California
Cherise Stanley: University of California
Krishan Aghi: University of California
Yang Joon Kim: University of California
Kevin Cao: University of California
Richard H. Kramer: University of California
Dirk Trauner: Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13
John Flannery: University of California
Ehud Y. Isacoff: University of California

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-01990-7

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