Retinal electrostimulation is promising a successful therapy to restore functional vision. However, a narrow stimulating current range exists between retinal neuron excitation and inhibition which may lead to misperformance of visual prostheses. As the conveyance of representation of complex visual scenes may require neighbouring electrodes to be activated simultaneously, electric field summation may contribute to reach this inhibitory threshold. This study used three approaches to assess the implications of relatively high stimulating conditions in visual prostheses: (1) in vivo, using a suprachoroidal prosthesis implanted in a feline model, (2) in vitro through electrostimulation of murine retinal preparations, and (3) in silico by computing the response of a population of retinal ganglion cells. Inhibitory stimulating conditions led to diminished cortical activity in the cat. Stimulus-response relationships showed non-monotonic profiles to increasing stimulating current. This was observed in vitro and in silico as the combined response of groups of neurons (close to the stimulating electrode) being inhibited at certain stimulating amplitudes, whilst other groups (far from the stimulating electrode) being recruited. These findings may explain the halo-like phosphene shapes reported in clinical trials and suggest that simultaneous stimulation in retinal prostheses is limited by the inhibitory threshold of the retinal ganglion cells.

In order to improve upon existing stimulation strategies for prosthetic vision, it is essential to assess stimulation effectiveness by measuring the responses of stimulated cells in retinal tissue. Calcium imaging has slower dynamics and lower signal-to-noise ratio than electrophysiological techniques. However, it has the ability to record responses from a large number of neurons, and is able to monitor responses from neurites too small for patch electrodes. We extended previous techniques of bulk loading RGC somata with organic calcium indicator to achieve staining of RGC dendritic processes and imaged calcium signals in retinal ganglion cell somata and dendrites simultaneously. The higher signal-to-noise ratio dendritic calcium signals make dendrites more suitable imaging regions for recording retinal ganglion cell responses to electrical stimulation protocols that are relevant to driving visual prosthetic stimulation.