Photovoltaic retinal prostheses theoretically offer the possibility of stand-alone high-resolution electrical stimulation of the retina. However, achieving focused epiretinal stimulation is particularly challenging because of axonal activation and electrical cell coupling. Recent evidence shows that long electric pulses permit a more focal activation of retinal ganglion cells, and non-rectangular waveforms induce higher network-mediated indirect activity.
The role of the pulse shape in focusing the retinal ganglion cell activation and the underlying mechanisms are not yet fully understood.
To address this question, we implemented a hybrid ex vivo and in silico approach. We recorded the evoked activity of retinas explanted from retinal degeneration ten mice upon photovoltaic and electrical stimulation with rectangular or non-rectangular capacitive-like voltage pulses. We used a biophysical model to investigate the role of the pulse shape and the pulse duration on the genesis and the extent of the network-mediated activity in retinal ganglion cells.
Altogether, our results suggest that non-rectangular capacitive-like voltage pulses activate more strongly the inner excitatory and inhibitory layers of the retina, when compared to a rectangular stimulation with paired pulse amplitude and duration. This feature leads to an increase of the network-mediated activity and a decrease in the network-mediated electrical receptive field of the stimulated retinal ganglion cell.
These results demonstrate that recruiting the inner retinal cells with epiretinal stimulation enables us not only to bypass axonal stimulation, but also to obtain a more focal activation due to the natural lateral inhibition. The involvement of the inhibitory feedback from amacrine cells in the genesis of the network-mediated activity represents a novel biological tool with which to confine the response of the retinal ganglion cells. These results support future waveform engineering strategies and offer new perspectives on epiretinal devices to better shape prosthetic perception.