Response of Human Retinal Networks to Electrical Stimulation using 3D Intra-retinal Microelectrodes

This research presents a computational model of the human retina's response to electrical stimulation using three-dimensional penetrating electrodes. Our model suggests that varying depths of insertion, coupled with specific stimulation parameters, can maximize the control over retinal ganglion cells. Notably, intra-retinal electrodes positioned in the inner plexiform layer can selectively modulate both ON and OFF functional pathways via direct activation of AII amacrine cells. In contrast, electrodes reaching the inner nuclear layer can indirectly inhibit the OFF pathway via gap junction coupling between bipolar cells and AII amacrine cells, and directly activate the ON pathway via ON bipolar cells. Furthermore, our simulations provide insights into the multi-faceted mechanisms underlying the differential retinal responses to intraretinal electrical stimulation. These mechanisms include differentially targeted neural subtypes and variations in the number of pre-synaptic neurons. New technologies capable of selective stimulation of different functional retinal pathways offer further hope to improve the level of artificial vision provided to blind patients. This powerful model allows us to assess how novel electrode and stimulation parameters influence retinal network electrical activity, guiding future development of more sophisticated retinal prosthetic devices and stimulation strategies to maximize therapeutic efficacy.