Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool

PLoS Biol. 2015 May 7;13(5):e1002143. doi: 10.1371/journal.pbio.1002143. eCollection 2015 May.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blindness / therapy*
  • Genetic Therapy / methods*
  • HEK293 Cells
  • Humans
  • Mice, Inbred C3H
  • Mice, Transgenic
  • Optogenetics / methods*
  • Receptors, Metabotropic Glutamate / administration & dosage
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism*
  • Retinal Bipolar Cells / drug effects
  • Retinal Bipolar Cells / metabolism*
  • Rod Opsins / administration & dosage
  • Rod Opsins / genetics
  • Rod Opsins / metabolism*
  • Vision, Ocular
  • Visual Perception


  • Receptors, Metabotropic Glutamate
  • Rod Opsins
  • melanopsin
  • metabotropic glutamate receptor 6

Grant support

This work was supported by sponsorship from the Haag-Streit Holding AG (HSH: and grants from the Swiss National Science Foundation (, 31003A_152807/1), the Commission for Technology and Innovation of Switzerland (, 14341.1 PFLS-LS), the Federal Ministry of Education and Research of Germany (, 01GQ0921 and 01GQ0810), the Deutsche Forschungsgemeinschaft ( through the Collaborative Research Center 889 to SL (Project B5) and an Alexander von Humboldt Research Fellowship for Postdoctoral Researchers to JPF. The funders had no role in study design, data collection and analysis, preparation of the manuscript or decision to publish.