gms | German Medical Science

Objective: Based on previous computational results we experimentally evaluated the possibility of focal activation of retinal ganglion cells (RGCs) by epiretinal stimulation using short pulse stimulation.

Materials and Methods: Spiking activity from RGCs in the wild-type (wt) and photoreceptor-degenerated (rd10) ex-vivo mouse retina was recorded using patch-clamp electrophysiology. Electrical stimulation was applied via a 10 kOhm microelectrode; the z-distance between targeted cells and stimulation electrode was adjusted to ~10 μm. The electrode was positioned either above the soma or at the distal axon. Axon trajectory was determined by filling cells with fluorescent dye followed by live fluorescent microscopy. Multicompartment models of RGCs were based on traced mouse alpha RGCs from previous studies.

Results: Action potentials could be reliably generated by electrical stimulation with charge balanced biphasic pulses 10–500μs in duration. Activation threshold was determined as the stimulus amplitude that led to an action potential in 66% of trials. Thresholds were comparable in wt and rd10 RGCs at both the soma and the axon. Stimulation at the soma resulted in lower thresholds for all pulse durations with shortest pulses maximizing the axon-to-soma threshold ratio from ~2–5 for 500 and 10 μs pulses, respectively. Additional simulations revealed polarization along the z-axis of the soma to be the underlying mechanism for lower thresholds at the soma.

Discussion: Our results reveal that stimulation with pulses in the range of 10 μs avoid the unwanted activation of passing axons in the ex-vivo mouse retina. Future research is needed to establish if the concept will translate to epiretinal implants in humans.

Acknowledgment: Research was supported by the Austrian Science Fund (FWF, P35488).