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

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 retin...

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Autores principales: van Wyk, Michiel, Pielecka-Fortuna, Justyna, Löwel, Siegrid, Kleinlogel, Sonja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423780/
https://www.ncbi.nlm.nih.gov/pubmed/25950461
http://dx.doi.org/10.1371/journal.pbio.1002143
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author van Wyk, Michiel
Pielecka-Fortuna, Justyna
Löwel, Siegrid
Kleinlogel, Sonja
author_facet van Wyk, Michiel
Pielecka-Fortuna, Justyna
Löwel, Siegrid
Kleinlogel, Sonja
author_sort van Wyk, Michiel
collection PubMed
description 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.
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spelling pubmed-44237802015-05-13 Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool van Wyk, Michiel Pielecka-Fortuna, Justyna Löwel, Siegrid Kleinlogel, Sonja PLoS Biol Research Article 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. Public Library of Science 2015-05-07 /pmc/articles/PMC4423780/ /pubmed/25950461 http://dx.doi.org/10.1371/journal.pbio.1002143 Text en © 2015 van Wyk et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
van Wyk, Michiel
Pielecka-Fortuna, Justyna
Löwel, Siegrid
Kleinlogel, Sonja
Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool
title Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool
title_full Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool
title_fullStr Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool
title_full_unstemmed Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool
title_short Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool
title_sort restoring the on switch in blind retinas: opto-mglur6, a next-generation, cell-tailored optogenetic tool
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423780/
https://www.ncbi.nlm.nih.gov/pubmed/25950461
http://dx.doi.org/10.1371/journal.pbio.1002143
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