Dampening spontaneous activity improves the light sensitivity and spatial acuity of optogenetic retinal prosthetic responses

John Martin Barrett*, Gerrit Hilgen, Evelyne Sernagor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
7 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number33565
Pages (from-to)1-19
Number of pages19
JournalScientific Reports
Volume6
Early online date21 Sep 2016
DOIs
Publication statusPublished - Dec 2016
Externally publishedYes

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