Network-mediated responses of ON ganglion cells to electric stimulation become less consistent across trials during retinal degeneration

Microelectronic retinal prostheses are being developed to restore sight in individuals blinded by outer retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Unfortunately, the quality of vision restored by these devices is still limited. To improve the quality of elicited vision, our group studies the responses of retinal neurons to electric stimulation. Our previous work showed that responses mediated through the retinal network are reproducible with high temporal precision, even for spikes that occur >100 ms after stimulus onset. Because they arise through the network, it is important to understand whether such reliability changes in the degenerate retina. Here, we examined response variability at several different stages of degeneration: postnatal day 14 (P14), P18, P31 and P60 in a well-established mouse model of degeneration (rd10). Spiking responses of ON alpha RGCs were recorded multiple times to an identical electric stimulus. We found that the trial-to-trial variability increased over the course of retinal degeneration. This finding may help to explain the reported variability in the quality of elicited vision across subjects using these devices.