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

Journal Article · · Nature Communications
 [1];  [2];  [2];  [3];  [4];  [2];  [2];  [5];  [6];  [2];  [7];  [8];  [9];  [10]
  1. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Oregon Health and Science Univ., Portland, OR (United States). Dept. of Medicine; DOE/OSTI
  2. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
  3. Ludwig Maximilian Univ. of Munich, Munich (Germany). Dept. of Chemistry. Munich Center for Integrated Protein Science; Ecole Polytechnique Federale Lausanne (Switzlerland). Sciences de base. Inst. des sciences et ingenierie chimiqes. Lab. of Protein Engineering
  4. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; ETH Zurich, Basel (Switzerland). Dept. of Biosystems Science Engineering
  5. Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
  6. Univ. of California, Berkeley, CA (United States). Biophysics Graduate Program
  7. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
  8. Ludwig Maximilian Univ. of Munich, Munich (Germany). Dept. of Chemistry. Munich Center for Integrated Protein Science
  9. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Univ. of California, Berkeley, CA (United States). School of Optometry
  10. Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.; Univ. of California, Berkeley, CA (United States). Biophysics Graduate Program; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Bioscience Division
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.
Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1624060
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 8; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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Shedding light on metabotropic glutamate receptors using optogenetics and photopharmacology journal February 2018
Conditional and Reversible Activation of Class A and B G Protein-Coupled Receptors Using Tethered Pharmacology journal January 2018
Photoreversible Soft Azo Dye Materials: Toward Optical Control of Bio‐Interfaces journal May 2019
Restoration of high-sensitivity and adapting vision with a cone opsin journal March 2019
Optical tools for understanding the complexity of β-cell signalling and insulin release journal October 2018
Optical control of neuronal ion channels and receptors journal July 2019
Next-generation interfaces for studying neural function journal August 2019
Optogenetic vision restoration with high resolution posted_content November 2018
Restoration of high-sensitivity and adapting vision with a cone opsin text January 2020
Innovative Optogenetic Strategies for Vision Restoration journal September 2018
Restoration of high-sensitivity and adapting vision with a cone opsin text January 2019
Optogenetic vision restoration with high resolution preprint January 2018

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