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Title: Restoration of high-sensitivity and adapting vision with a cone opsin

Abstract

Inherited and age-related retinal degenerative diseases cause progressive loss of rod and cone photoreceptors, leading to blindness, but spare downstream retinal neurons, which can be targeted for optogenetic therapy. However, optogenetic approaches have been limited by either low light sensitivity or slow kinetics, and lack adaptation to changes in ambient light, and not been shown to restore object vision. We find that the vertebrate medium wavelength cone opsin (MW-opsin) overcomes these limitations and supports vision in dim light. MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light. By contrast, rhodopsin, which is similar in sensitivity but slower in light response and has greater rundown, fails these tests. Thus, MW-opsin provides the speed, sensitivity and adaptation needed to restore patterned vision.

Authors:
ORCiD logo [1];  [2];  [2];  [2];  [2];  [2]; ORCiD logo [2];  [2];  [3]; ORCiD logo [2];  [4]
  1. Univ. of California, Berkeley, CA (United States); Oregon Health and Sciences Univ., Portland, OR (United States)
  2. Univ. of California, Berkeley, CA (United States)
  3. Oregon Health and Sciences Univ., Portland, OR (United States)
  4. Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1559194
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Berry, Michael H., Holt, Amy, Salari, Autoosa, Veit, Julia, Visel, Meike, Levitz, Joshua, Aghi, Krisha, Gaub, Benjamin M., Sivyer, Benjamin, Flannery, John G., and Isacoff, Ehud Y. Restoration of high-sensitivity and adapting vision with a cone opsin. United States: N. p., 2019. Web. doi:10.1038/s41467-019-09124-x.
Berry, Michael H., Holt, Amy, Salari, Autoosa, Veit, Julia, Visel, Meike, Levitz, Joshua, Aghi, Krisha, Gaub, Benjamin M., Sivyer, Benjamin, Flannery, John G., & Isacoff, Ehud Y. Restoration of high-sensitivity and adapting vision with a cone opsin. United States. doi:10.1038/s41467-019-09124-x.
Berry, Michael H., Holt, Amy, Salari, Autoosa, Veit, Julia, Visel, Meike, Levitz, Joshua, Aghi, Krisha, Gaub, Benjamin M., Sivyer, Benjamin, Flannery, John G., and Isacoff, Ehud Y. Fri . "Restoration of high-sensitivity and adapting vision with a cone opsin". United States. doi:10.1038/s41467-019-09124-x. https://www.osti.gov/servlets/purl/1559194.
@article{osti_1559194,
title = {Restoration of high-sensitivity and adapting vision with a cone opsin},
author = {Berry, Michael H. and Holt, Amy and Salari, Autoosa and Veit, Julia and Visel, Meike and Levitz, Joshua and Aghi, Krisha and Gaub, Benjamin M. and Sivyer, Benjamin and Flannery, John G. and Isacoff, Ehud Y.},
abstractNote = {Inherited and age-related retinal degenerative diseases cause progressive loss of rod and cone photoreceptors, leading to blindness, but spare downstream retinal neurons, which can be targeted for optogenetic therapy. However, optogenetic approaches have been limited by either low light sensitivity or slow kinetics, and lack adaptation to changes in ambient light, and not been shown to restore object vision. We find that the vertebrate medium wavelength cone opsin (MW-opsin) overcomes these limitations and supports vision in dim light. MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light. By contrast, rhodopsin, which is similar in sensitivity but slower in light response and has greater rundown, fails these tests. Thus, MW-opsin provides the speed, sensitivity and adaptation needed to restore patterned vision.},
doi = {10.1038/s41467-019-09124-x},
journal = {Nature Communications},
number = 1,
volume = 10,
place = {United States},
year = {2019},
month = {3}
}

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