Purchase this article with an account.
D. Balya, V. Busskamp, J. Duebel, M. W. Seeliger, P. Humphries, M. Biel, K. Deisseroth, J. A. Sahel, S. A. Picaud, B. Roska; Genetic Reactivation of Cone Photoreceptors Restores Complex Visual Responses in Retinitis Pigmentosa - Part 3. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3297.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
In retinal degenerative diseases like Retinitis pigmentosa (RP) rod photoreceptors die early. Light-insensitive, morphologically altered cone photoreceptors persist. It is unknown if these cones are accessible for therapeutic interventions. We evaluated the potential of a red-light sensitive chloride pump in cones to substitute for the native phototransduction cascade and restore their light sensitivity in mouse models of RP.
We used adeno-associated-virus (AAV)-mediated gene transfer to express an archaebacterial halorhodopsin (eNpHR) specifically in cones in two mouse models of RP (poster part 1). To test if eNpHR is functional in treated retinas we recorded light responses (poster part 2) from photoreceptors, ganglion cells and the visual cortex, and performed behavioral experiments.
Resensitized photoreceptors activate retinal cone pathways, drive sophisticated retinal circuit functions including directional selectivity, activate cortical circuits and mediate visually guided behaviors. The increased performance depends on the level of illumination in the dark-light box. In the optomotor reflex test, treated mice perform better than control at a variety of drum speeds.
Our results demonstrate that, despite the diverse genetic origin of RP, the targeted expression of a single gene can restore significant functionality to the visual system following degenerative changes. Light-induced activity was observed at the ganglion cell level, in the visual cortex and at the behavioral level.
This PDF is available to Subscribers Only