Abstract
Purpose :
Epiretinal prosthetic systems have been developed to restore sight to the blind; however, the spatial resolution of current devices is still limited. Previous studies have demonstrated that long stimulus pulses (∼ 25 ms) or low sinusoidal frequencies (5-25 Hz) can selectively target retinal bipolar cells (BCs) and, therefore, improve the spatial resolution of epiretinal implants by avoiding axonal activation of retinal ganglion cells (RGCs). In this study, we present a computational modeling framework that captures the biophysical factors that influence the stimulus threshold of BCs to long stimulus pulse durations.
Methods :
Using the Admittance Method (AM)/NEURON computational platform, we implemented a model of spiking BCs, diffuse bipolar cell subtypes (DB4), that was verified with experimental and modeling data from the literature. We analyzed the response of BCs over a range of stimulus pulses, including cathodic monophasic and anodic-first biphasic pulses. We investigated the role of the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels at the presynaptic terminals in the high sensitivity of BCs to long stimulus pulse durations.
Results :
We tested a range of pulse durations from 0.1 ms to 25 ms and compared the response of BCs to cathodic monophasic and anodic-first biphasic pulses. Our data show that long anodic-first biphasic pulse durations (> 8 ms) significantly reduce the stimulus threshold of BCs relative to long cathodic-first pulses from 98 µA to 57 µA. We further explored that the absence of HCN channels at the presynaptic terminals of BCs increases the stimulus threshold of BCs and, therefore, HCN channels contribute to the higher sensitivity of BCs to long anodic-first stimulus pulse widths.
Conclusions :
Our computational findings suggest that the presence of long anodic pulses prior to cathodic pulses likely contributes to selective activation of BCs and the reported rounder shape of phosphene with epiretinal implants using long stimulus pulse widths. The reduced threshold and high sensitivity of BCs to low-frequency stimulation and long pulse durations are likely mediated by the high concentration of HCN channels at the terminals of BCs.
This is a 2021 ARVO Annual Meeting abstract.