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Curr Biol. 2015 Aug 17;25(16):2111-22. doi: 10.1016/j.cub.2015.07.029. Epub 2015 Jul 30.

Restoration of Vision with Ectopic Expression of Human Rod Opsin.

Author information

1
Centre for Ophthalmology and Vision Sciences, Institute of Human Development, University of Manchester, Manchester M13 9PT, UK; Manchester Royal Eye Hospital, CMFT, Manchester Academic Health Sciences Centre, Manchester M13 9NT, UK.
2
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
3
Centre for Ophthalmology and Vision Sciences, Institute of Human Development, University of Manchester, Manchester M13 9PT, UK; Manchester Royal Eye Hospital, CMFT, Manchester Academic Health Sciences Centre, Manchester M13 9NT, UK. Electronic address: paul.bishop@manchester.ac.uk.
4
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK. Electronic address: robert.lucas@manchester.ac.uk.

Abstract

Many retinal dystrophies result in photoreceptor loss, but the inner retinal neurons can survive, making them potentially amenable to emerging optogenetic therapies. Here, we show that ectopically expressed human rod opsin, driven by either a non-selective or ON-bipolar cell-specific promoter, can function outside native photoreceptors and restore visual function in a mouse model of advanced retinal degeneration. Electrophysiological recordings from retinal explants and the visual thalamus revealed changes in firing (increases and decreases) induced by simple light pulses, luminance increases, and naturalistic movies in treated mice. These responses could be elicited at light intensities within the physiological range and substantially below those required by other optogenetic strategies. Mice with rod opsin expression driven by the ON-bipolar specific promoter displayed behavioral responses to increases in luminance, flicker, coarse spatial patterns, and elements of a natural movie at levels of contrast and illuminance (≈50-100 lux) typical of natural indoor environments. These data reveal that virally mediated ectopic expression of human rod opsin can restore vision under natural viewing conditions and at moderate light intensities. Given the inherent advantages in employing a human protein, the simplicity of this intervention, and the quality of vision restored, we suggest that rod opsin merits consideration as an optogenetic actuator for treating patients with advanced retinal degeneration.

KEYWORDS:

rhodopsin

PMID:
26234216
PMCID:
PMC4540256
DOI:
10.1016/j.cub.2015.07.029
[Indexed for MEDLINE]
Free PMC Article

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