Evidence map›Paper›PMID 26137852›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015

Optogenetic Vision Restoration Using Rhodopsin for Enhanced Sensitivity.

Benjamin M Gaub, Michael H Berry, Amy E Holt, Ehud Y Isacoff, John G Flannery

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
6.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Optogenetic vision restoration in the face of secondary and tertiary remodeling in the rd1 mouse retina.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Optogenetic Vision Restoration.Cold Spring Harbor perspectives in medicine · 2024
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
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22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Benjamin M GaubHelen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, USA.
Michael H BerryDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA.
Amy E HoltDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA.
Ehud Y IsacoffHelen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, USA.
John G FlanneryHelen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California, USA.
University of California, Berkeley · USLawrence Berkeley National Laboratory · US

Funding

NDC for the Optical Control of Biological FunctionPN2EY018241 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD · 2006 to 2015
$37.5M
MODELS OF HEREDITY RETINAL DEGENERATIONR01EY006855 · NEI · UNIVERSITY OF PENNSYLVANIA · PI GUSTAVO David AGUIRRE, William A. Beltran · 1992 to 2026
$20.7M
Scientific TransparencyP30EY001583 · NEI · UNIVERSITY OF PENNSYLVANIA · PI CLAIRE H MITCHELL · 1985 to 2026
$19.5M
Optical Control of Synaptic Transmission for in Vivo Analysis of Brain Circuits and BehaviorU01NS090527 · NINDS · UNIVERSITY OF CALIFORNIA BERKELEY · PI ISACOFF, EHUD, KRAMER, RICHARD H · 2014 to 2016
$2.4M
CONVERTING BIPOLAR CELLS INTO RED-SHIFTED OPTOGENETIC SENSORS FOR RETINAL THERAPYR01EY024958 · NEI · WASHINGTON UNIVERSITY · PI CORBO, JOSEPH, FLANNERY, JOHN GERARD · 2015 to 2019
$2.2M
Directed Evolution of Adeno-Associated Virus for Retinal Gene TherapyR01EY022975 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI FLANNERY, JOHN GERARD, SCHAFFER, DAVID V · 2014 to 2018
$2.1M
NEI NIH HHS P30EY-NEI NIH HHS P30 EY001583NEI NIH HHS PN2 EY018241NEI NIH HHS PN2EY018241NEI NIH HHS R01 EY006855NEI NIH HHS R01 EY022975NEI NIH HHS R01 EY024958NEI NIH HHS R01EY06855NINDS NIH HHS U01 NS090527
6 · The paper itself

Abstract

Retinal disease is one of the most active areas of gene therapy, with clinical trials ongoing in the United States for five diseases. There are currently no treatments for patients with late-stage disease in which photoreceptors have been lost. Optogenetic gene therapies are in development, but, to date, have suffered from the low light sensitivity of microbial opsins, such as channelrhodopsin and halorhodopsin, and azobenzene-based photoswitches. Several groups have shown that photoreceptive G-protein-coupled receptors (GPCRs) can be expressed heterologously, and photoactivate endogenous Gi/o signaling. We hypothesized such a GPCR could increase sensitivity due to endogenous signal amplification. We targeted vertebrate rhodopsin to retinal ON-bipolar cells of blind rd1 mice and observed restoration of: (i) light responses in retinal explants, (ii) visually-evoked potentials in visual cortex in vivo, and (iii) two forms of visually-guided behavior: innate light avoidance and discrimination of temporal light patterns in the context of fear conditioning. Importantly, both the light responses of the retinal explants and the visually-guided behavior occurred reliably at light levels that were two to three orders of magnitude dimmer than required for channelrhodopsin. Thus, gene therapy with native light-gated GPCRs presents a novel approach to impart light sensitivity for visual restoration in a useful range of illumination.

Indexed as

AnimalsDependovirusEctopic Gene ExpressionEvoked Potentials, VisualGenetic TherapyGenetic VectorsLightMiceOptogeneticsPhotic StimulationRetinaRetinal Bipolar CellsRetinal Ganglion CellsRhodopsinTransduction, GeneticVision, OcularRhodopsin

Identifiers

PMID26137852
PMCPMC4817926
OpenAlexW836249930

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.