Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor
Journal Article
·
· Nature Communications
- 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
- Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
- 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
- Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; ETH Zurich, Basel (Switzerland). Dept. of Biosystems Science Engineering
- Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
- Univ. of California, Berkeley, CA (United States). Biophysics Graduate Program
- Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology; Univ. of California, Berkeley, CA (United States). Helen Wills Neuroscience Inst.
- Ludwig Maximilian Univ. of Munich, Munich (Germany). Dept. of Chemistry. Munich Center for Integrated Protein Science
- 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
- 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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