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; Kevin Cao; Richard H Kramer; Dirk Trauner; John Flannery; Ehud Y Isacoff

doi:10.1038/s41467-017-01990-7

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

Nat Commun. 2017 Nov 30;8(1):1862. doi: 10.1038/s41467-017-01990-7.

Authors

Michael H Berry^{1

2}, Amy Holt¹, Joshua Levitz^{1

3}, Johannes Broichhagen^{4

5

6}, Benjamin M Gaub^{1

7}, Meike Visel¹, Cherise Stanley¹, Krishan Aghi⁸, Yang Joon Kim⁹, Kevin Cao¹, Richard H Kramer^{1

8}, Dirk Trauner^{4

10}, John Flannery^{1

8

11}, Ehud Y Isacoff^{12

13

14

15}

Affiliations

¹ Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.
² Department of Medicine, Oregon Health and Science University, Portland, OR, 97239, USA.
³ Department of Biochemistry, Weill Cornell Medical College, New York City, New York, 10024, USA.
⁴ Department of Chemistry, Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377, München, Germany.
⁵ Laboratory of Protein Engineering, Institut des sciences et ingénierie chimiques, Sciences de base, École Polytechnique Fédérale Lausanne, 1015, Lausanne, Switzerland.
⁶ Department of Chemical Biology, Max-Planck Institute for Medical Research, Jahnstr. 29, 69120, Heidelberg, Germany.
⁷ Department of Biosystems Science Engineering, ETH Zürich, Mattenstrasse 26, 4058, Basel, Switzerland.
⁸ Helen Wills Neuroscience Institute, University of California, Berkeley, CA, 94720, USA.
⁹ Biophysics Graduate Program, University of California, Berkeley, CA, 94720, USA.
¹⁰ Department of Chemistry, New York University, New York City, New York, 10003, USA.
¹¹ School of Optometry, University of California, Berkeley, CA, 94720, USA.
¹² Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA. ehud@berkeley.edu.
¹³ Helen Wills Neuroscience Institute, University of California, Berkeley, CA, 94720, USA. ehud@berkeley.edu.
¹⁴ Biophysics Graduate Program, University of California, Berkeley, CA, 94720, USA. ehud@berkeley.edu.
¹⁵ Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA. ehud@berkeley.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Disease Models, Animal
Light*
Mice
Photoreceptor Cells, Vertebrate / metabolism*
Photoreceptor Cells, Vertebrate / physiology
Protein Engineering*
Receptors, Glutamate / metabolism*
Receptors, Ionotropic Glutamate
Receptors, Metabotropic Glutamate / chemistry
Receptors, Metabotropic Glutamate / genetics*
Receptors, Metabotropic Glutamate / metabolism
Retina / metabolism*
Retina / physiology
Retinal Ganglion Cells / metabolism*
Retinal Ganglion Cells / physiology
Retinitis Pigmentosa
Vision, Ocular / physiology*
Visual Acuity*

Substances

LiGluR receptor
Receptors, Glutamate
Receptors, Ionotropic Glutamate
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding