Contributed Session I: Foveal RGCs develop abnormal calcium clearance weeks after photoreceptor ablation.

Abstract

Vision restoration therapies aim to restore light sensitivity to the retina following photoreceptor (PR) degeneration. Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of PR loss but this has not been investigated in primates. By expressing both a calcium indicator (GCaMP6s) and an optogenetic actuator (ChrimsonR) in foveal RGCs of a macaque, we reactivate RGCs and assess activity in the weeks and years following PR loss. Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 s optogenetic stimulus (1 mW, 640 nm) was delivered to the deafferented RGCs, and GCaMP fluorescence was recorded for 90 s. The calcium response was collected with AOSLO over 10 weeks and the signal decay was fitted with an exponential model. Optogenetic responses in RGCs persisted over 2 years following PR ablation. The mean time to peak calcium response was stable in deafferented RGCs over the 10 weeks (paired t-test, p<0.001), while the mean decay constant of the calcium response decreased 2.1 fold (2.5±0.5 s to 1.2±0.2 s SD) in the 8 weeks post PR ablation. The presence of optogenetic responses 2 years after PR loss and the stable rise time is promising for vision restoration therapies with RGCs. However, the 2-fold reduction in the decay constant of the calcium response suggests that restored activity may be impacted by physiological changes in the inner retina weeks after PR loss.