The effect of axon trajectory on retinal ganglion cell activation with epiretinal stimulation

For epiretinal prostheses, disc electrodes stimulate retinal ganglion cells (RGCs) with electric current to create visual percepts. Prior studies have determined that the sodium channel band (SOCB), located on the RGC axon (30-50 μm from the soma) is the most sensitive site to extracellular stimulation because of its high sodium channel density. Biophysical cable models used to study RGC activation in silico often rely on simplified axon trajectories, disregarding the non-uniform paths that axons follow to the optic disc. However, since axonal activation is a critical mechanism in epiretinal stimulation, it is important to investigate variable RGC axon trajectories. In this study, we use a computational model to perform a sensitivity analysis examining how the morphology of an RGC axon affects predictions of retinal activation. We determine that RGC cable models are sensitive to changes in the ascending axon trajectory between the soma and nerve fiber layer. On the other hand, RGC cable models are relatively robust to trajectory deviations in the plane parallel to the disc electrode's surface. Overall, our results suggest that incorporating natural variations of soma depth and nerve fiber layer entry angle could result in a more realistic model of the retina's response to epiretinal stimulation and a better understanding of elicited visual percepts.