Restoration of patterned vision with an engineered
photoactivatable G protein-coupled receptor
Michael H. Berry
, Amy Holt
, Joshua Levitz
, Johannes Broichhagen
, Benjamin M. Gaub
, Cherise Stanley
, Krishan Aghi
, Yang Joon Kim
, Kevin Cao
, Richard H. Kramer
, John Flannery
& Ehud Y. Isacoff
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 perpen-
dicular 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.
Corrected: Author correction
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Department of Medicine, Oregon Health and Science
University, Portland, OR 97239, USA.
Department of Chemistry, Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein
Science, Butenandtstrasse 5-13, 81377 München, Germany.
Laboratory of Protein Engineering, Institut des sciences et ingénierie chimiques, Sciences de
base, École Polytechnique Fédérale Lausanne, 1015 Lausanne, Switzerland.
Department of Biosystems Science Engineering, ETH Zürich, Mattenstrasse 26,
4058 Basel, Switzerland.
Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
Biophysics Graduate Program, University
of California, Berkeley, CA 94720, USA.
School of Optometry, University of California, Berkeley, CA 94720, USA.
Bioscience Division, Lawrence Berkeley
National Laboratory, Berkeley, CA 94720, USA.
Present address: Department of Biochemistry, Weill Cornell Medical College, New York City, New York
Present address: Department of Chemical Biology, Max-Planck Institute for Medical Research, Jahnstr. 29, 69120 Heidelberg, Germany.
Present address: Department of Chemistry, New York University, New York City, New York 10003, USA. Correspondence and requests for materials should
be addressed to E.Y.I. (email: firstname.lastname@example.org)