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

Berry, Michael H.; Holt, Amy; Levitz, Joshua; Broichhagen, Johannes; Gaub, Benjamin M.; Visel, Meike; Stanley, Cherise; Aghi, Krishan; Kim, Yang Joon; Trauner, Dirk; Flannery, John; Isacoff, Ehud Y. (2017): Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor. In: Nature Communications, Vol. 8, 1862

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.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Chemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 2041-1723
• Language: English