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Improved daylight vision following AAV-mediated expression of R9AP in murine rod photoreceptors

Nishiguchi, K. M.; Fujita, K.; Cristante, E.; Bainbridge, J. W.; Douglas, R. H.; Nakazawa, T.; Smith, A.; Ali, R. R.

2020-02-20 bioengineering
10.1101/2020.02.19.955765 bioRxiv
Show abstract

Cone photoreceptors mediate daylight vision and are the primary cells responsible for vision in humans. Cone dysfunction leads to poor quality daylight vision because rod photoreceptors become saturated and non-functional at high light levels. Here we demonstrate that in mice lacking cone function, AAV-mediated over-expression of Rgs9-anchor protein (R9AP), a critical component of the GTPase complex that mediates the deactivation of the phototransduction cascade, results in desensitization of rod function and a "photopic shift" of the rod-driven electroretinogram. This treatment enables rods to respond to brighter light (up to [~]2.0 log) with increased visually-evoked cortical responses to high intensity stimulation. These results suggest that AAV-mediated transfer of R9ap into rods might be used to improve daylight vision in humans visually handicapped by cone dysfunction.

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