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, Dirk Trauner, John Flannery, Ehud Y. Isacoff

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1862
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

G-Protein-Coupled Receptors
restoration
Restoration
proteins
Light
photoreceptors
Retinal Ganglion Cells
cells
blindness
visual acuity
acuity
Ionotropic Glutamate Receptors
glutamates
Retinitis Pigmentosa
degeneration
retina
Blindness
Prosthetics
Visual Acuity
logic

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Berry, M. H., Holt, A., Levitz, J., Broichhagen, J., Gaub, B. M., Visel, M., ... Isacoff, E. Y. (2017). Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor. Nature Communications, 8(1), [1862]. https://doi.org/10.1038/s41467-017-01990-7

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.

In: Nature Communications, Vol. 8, No. 1, 1862, 01.12.2017.

Research output: Contribution to journalArticle

Berry, MH, Holt, A, Levitz, J, Broichhagen, J, Gaub, BM, Visel, M, Stanley, C, Aghi, K, Kim, YJ, Trauner, D, Flannery, J & Isacoff, EY 2017, 'Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor', Nature Communications, vol. 8, no. 1, 1862. https://doi.org/10.1038/s41467-017-01990-7
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. / Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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