title: Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool.
abstract: Photoreceptor degeneration is one of the most prevalent causes of blindness. Despite photoreceptor loss, the inner retina and central visual pathways remain intact over an extended time period, which has led to creative optogenetic approaches to restore light sensitivity in the surviving inner retina. The major drawbacks of all optogenetic tools recently developed and tested in mouse models are their low light sensitivity and lack of physiological compatibility. Here we introduce a next-generation optogenetic tool, Opto-mGluR6, designed for retinal ON-bipolar cells, which overcomes these limitations. We show that Opto-mGluR6, a chimeric protein consisting of the intracellular domains of the ON-bipolar cell-specific metabotropic glutamate receptor mGluR6 and the light-sensing domains of melanopsin, reliably recovers vision at the retinal, cortical, and behavioral levels under moderate daylight illumination.
authors.affiliation: Institute for Physiology, University of Bern, Bern, Switzerland; Institute for Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Michiel
authors.initials: M
authors.lastname: van Wyk
authors.affiliation: Systems Neuroscience, Bernstein Fokus Neurotechnology and Johann-Friedrich-Blumenbach Institut für Zoologie und Anthropologie, Universität Göttingen, Von-Siebold-Str. 6, Göttingen, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Pielecka-Fortuna
authors.affiliation: Systems Neuroscience, Bernstein Fokus Neurotechnology and Johann-Friedrich-Blumenbach Institut für Zoologie und Anthropologie, Universität Göttingen, Von-Siebold-Str. 6, Göttingen, Germany; Sensory Collaborative Research Center 889, University of Göttingen, Göttingen, Germany.
authors.forename: Siegrid
authors.initials: S
authors.lastname: Löwel
authors.affiliation: Institute for Physiology, University of Bern, Bern, Switzerland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kleinlogel
mesh_terms: D000818:Animals; D001766:Blindness / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D062308:Optogenetics / Q000379:methods*; D018094:Receptors, Metabotropic Glutamate / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000378:metabolism*; D017299:Rod Opsins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D014785:Vision, Ocular; D014796:Visual Perception; D000099210:Melanopsin
chemical_list: D018094:Receptors, Metabotropic Glutamate; D017299:Rod Opsins; D000099210:Melanopsin; C113897:metabotropic glutamate receptor 6