Sodium channel inactivation reduces retinal ganglion cell responsiveness to repetitive prosthetic stimulation

Several research groups are developing retinal implants for restoring sight to the profoundly blind. These devices are able to elicit simple percepts. However, recent human clinical studies have reported a frequency-dependent fading of electrically evoked percepts when stimulating at frequencies above several Hz. Studies using isolated retinas also observed a decline in RGC spiking response rate during repetitive stimulation. The mechanism(s) underlying this response rate decline could also contribute to the fading percepts in human patients. Using patch clamp recordings of rabbit retinas, we found a frequency-dependent inactivation of RGC voltage-gated sodium channels during repetitive stimulation at ≥ 50 Hz. This may have contributed to the RGC spiking response rate depression. Inhibition from the retinal network, however, did not have a significant effect on the response rate of these directly-activated RGCs.