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

  • Author(s): Berry, MH
  • Holt, A
  • Levitz, J
  • Broichhagen, J
  • Gaub, BM
  • Visel, M
  • Stanley, C
  • Aghi, K
  • Kim, YJ
  • Trauner, D
  • Flannery, J
  • Isacoff, EY
  • et al.

Published Web Location

http://doi.org/10.1038/s41467-017-01990-7
No data is associated with this publication.
Abstract

© 2017 The Author(s). 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.

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