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Dampening Spontaneous Activity Improves the Light Sensitivity and Spatial Acuity of Optogenetic Retinal Prosthetic Responses

Lookup NU author(s): John Barrett, Dr Gerrit HilgenORCiD, Professor Evelyne SernagorORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Retinitis pigmentosa is a progressive retinal dystrophy that causes irreversible visual impairment and blindness. Retinal prostheses currently represent the only clinically available vision-restoring treatment, but the quality of vision returned remains poor. Recently, it has been suggested that the pathological spontaneous hyperactivity present in dystrophic retinas may contribute to the poor quality of vision returned by retinal prosthetics by reducing the signal-to-noise ratio of prosthetic responses. Here, we investigated to what extent blocking this hyperactivity can improve optogenetic retinal prosthetic responses. We recorded activity from channelrhodopsin-expressing retinal ganglion cells in retinal wholemounts in a mouse model of retinitis pigmentosa. Sophisticated stimuli, inspired by those used in clinical visual assessment, were used to assess light sensitivity, contrast sensitivity and spatial acuity of optogenetic responses; in all cases these were improved after blocking spontaneous hyperactivity using meclofenamic acid, a gap junction blocker. Our results suggest that this approach significantly improves the quality of vision returned by retinal prosthetics, paving the way to novel clinical applications. Moreover, the improvements in sensitivity achieved by blocking spontaneous hyperactivity may extend the dynamic range of optogenetic retinal prostheses, allowing them to be used at lower light intensities such as those encountered in everyday life.

Publication metadata

Author(s): Barrett JM, Hilgen G, Sernagor E

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2016

Volume: 6

Online publication date: 21/09/2016

Acceptance date: 19/08/2016

Date deposited: 22/09/2016

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group


DOI: 10.1038/srep33565

PubMed id: 27650332


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Funder referenceFunder name
096975/Z/11/ZWellcome Trust
6008477th Framework Program for Research of the European Commission