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

Author

Listed:
  • Michael H. Berry

    (University of California
    Oregon Health and Science University)

  • Amy Holt

    (University of California)

  • Joshua Levitz

    (University of California
    Weill Cornell Medical College)

  • Johannes Broichhagen

    (Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13
    Institut des sciences et ingénierie chimiques, Sciences de base, École Polytechnique Fédérale Lausanne
    Max-Planck Institute for Medical Research, Jahnstr. 29)

  • Benjamin M. Gaub

    (University of California
    Department of Biosystems Science Engineering, ETH Zürich, Mattenstrasse 26)

  • Meike Visel

    (University of California)

  • Cherise Stanley

    (University of California)

  • Krishan Aghi

    (University of California)

  • Yang Joon Kim

    (University of California)

  • Kevin Cao

    (University of California)

  • Richard H. Kramer

    (University of California
    University of California)

  • Dirk Trauner

    (Ludwig-Maximilians-Universität München, and Munich Center for Integrated Protein Science, Butenandtstrasse 5-13
    New York University)

  • John Flannery

    (University of California
    University of California
    University of California)

  • Ehud Y. Isacoff

    (University of California
    University of California
    University of California
    Lawrence Berkeley National Laboratory)

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.

Suggested Citation

  • 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 & Jo, 2017. "Restoration of patterned vision with an engineered photoactivatable G protein-coupled receptor," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01990-7
    DOI: 10.1038/s41467-017-01990-7
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