TY - JOUR
T1 - Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor
AU - Berry, Michael H.
AU - Holt, Amy
AU - Levitz, Joshua
AU - Broichhagen, Johannes
AU - Gaub, Benjamin M.
AU - Visel, Meike
AU - Stanley, Cherise
AU - Aghi, Krishan
AU - Kim, Yang Joon
AU - Trauner, Dirk
AU - Flannery, John
AU - Isacoff, Ehud Y.
N1 - Funding Information:
We thank Leah Byrne, Cameron Baker, Prashant Donthamsetti, Autoosa Salari and Richard Kramer for helpful discussion and Adam Hoagland, Zhu Fu, Elizabeth Carroll, Drew Friedmann, Aleksandra Polosukhina, and Ivan Tochitsky for technical assistance. The work was supported by the National Institutes of Health Nanomedicine Center for the Optical Control of Biological Function (2PN2EY018241) (E.Y.I., J.F. and D.T.) and instrumentation award (S10 RR028971) and the National Science Foundation Major Research Instrumentation Award (1041078) and EAGER award (IOS-1451027) (E.Y.I.). We are grateful to the Centre for Integrated Protein Science Munich (CIPSM) (J.B. and D.T.), the ‘EPFL Fellows’ fellowship programme co-funded by Marie Skłodowska-Curie, Horizon 2020 (665667) (J.B.) and an Advanced Grant from the European Research Council (268795) (D.T.). We kindly thank Prof. Dr. Kai Johnsson for providing BG-and BC-containing compounds.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-01990-7
DO - 10.1038/s41467-017-01990-7
M3 - Article
C2 - 29192252
AN - SCOPUS:85037028168
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1862
ER -