title: Dampening Spontaneous Activity Improves the Light Sensitivity and Spatial Acuity of Optogenetic Retinal Prosthetic Responses.
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.
authors.affiliation: Institute of Neuroscience, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.
authors.forename: John Martin
authors.initials: JM
authors.lastname: Barrett
authors.affiliation: Institute of Neuroscience, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Hilgen
authors.affiliation: Institute of Neuroscience, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, United Kingdom.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Sernagor
mesh_terms: D000818:Animals; D000075402:Channelrhodopsins / Q000378:metabolism; D015350:Contrast Sensitivity / Q000528:radiation effects; D008027:Light; D051379:Mice; D062308:Optogenetics; D011188:Potassium / Q000494:pharmacology; D012160:Retina / Q000528:radiation effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014792:Visual Acuity / Q000528:radiation effects*; D057488:Visual Prosthesis
chemical_list: D000075402:Channelrhodopsins; D011188:Potassium