Visual acuity and optical flow in primate retinal ganglion cells treated with an optogenetic vision restoration strategy using ChrimsonR

Abstract

Purpose : Visual restoration has been shown to be a success in blind mice following photoreceptor degeneration by expressing microbial opsins in retinal ganglion cells (RGCs). Investigating the clinical translation of this optogenetic therapy, we recently showed that the AAV2.7m8–ChrimsonR-tdTomato viral construct can induce significant response in peri-foveal retinal ganglion cells of non-human primates. We have further investigated the performance of this optogenetic vision restoration strategy in terms of visual acuity of the retinal ganglion cells.

Methods : We performed ex-vivo multi-electrode array recordings from the peri-foveal retina of non-human primates under a high resolution light stimulation setup using digital micromirror display (DMD). RGCs were stimulated with bars of different sizes (25um and 50um) moving at 4 different orientations (0, 45 90, 135 w.r.t the DMD). We then compared cells responses to these moving bar stimuli in order to determine the minimum length of bar required for the cells to respond and estimate the direction of the bars. We further stimulated the retinal ganglion cells with different letters (E,X,T,P) and shapes (Circle and Square) of different sizes (55, 110, 227, 340.5um) moving over the retina at different angles at a speed of 11 degree/sec.

Results : We used a spatio-temporal event-based optical flow algorithm (already published) to compute the flow from the recorded spiking activity in the RGC population during moving bar stimuli to estimate the orientation, speed and direction of the motion of the bar. Individual RGCs could detect motion of small bars (25um) moving at a speed of 2.27mm/sec (equivalent to 11 deg/sec). The RGC population could estimate the orientation of the bar using algorithm upon an accuracy of 86.76 +- 2.05% (n=3). For letters and shapes, we computed the ability of the RGC population to discriminate stimuli of different sizes. Using information theory analysis, we found that that the RGC population could discriminate letters and shapes of greater than 110 um on the retina, which is above the limit of legal blindness.

Conclusions : These results provide an estimate of the visual performance possible in blind subjects that will undergo optogenetic vision restoration therapy with ChrimsonR-TdTomato. They suggest our optogenetic strategy could restore a visual ability above legal blindness.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.