"Optimisation of electrical stimulation in the retina of retinitis pigmentosa mouse model rd10"

The loss of photoreceptors during retinal degeneration diseases like retinitis pigmentosa (RP)leads to blindness. One of the therapeutic strategies to treat this disease is to electrically stimulate the remaining cells in the retina using a retinal implant. However, the effectiveness of retinal implants in the treatment of blindness falls behind expectations. In this study, I show different methods to optimise the electrical stimulation produced by an implant to improve its performance. In vitro recordings from the retina of a retinal degeneration mouse model, rd10, that mimics human RP, were used in this study. In the degenerated retina, an intrinsic oscillatory activity with rhythmic bursts in the action potential firing has been observed. The oscillations were shown to reduce the efficiency of electrical stimulation. Therefore, one way to improve the stimulation efficiency will be to abolish the oscillations. In this regard, I have tested several pharmacological drugs and found a GABAA receptor agonist, THIP, that can abolish oscillations and improve stimulation efficiency. This shows that an electro-pharmacological therapy is one of the solutions to improve the electrical stimulation of an implant. Another way to optimise electrical stimulation is to stimulate at certain phases in the oscillation. In the rd10recordings, we observed cells that have spikes phase-locked to the minima of the oscillation and cells with spikes that are not phase-locked. On stimulation at the maxima, a better response is elicited from the non-phase-locked spiking cells. Therefore, applying electrical stimulation in a temporarily restricted manner to stimulate the non-phase-locked spiking cells would produce a better response from a degenerated retina. The current retinal prostheses do not differentiate between the different retinal ganglion cells (RGCs), like the ON RGCs, which are active with light, and OFF RGCs, which are active in the dark. Equal activation would affect the resolution of the image and cause a mixed response. Here, I had identified certain shapes, amplitudes and durations of the electrical pulse that would selectively excite ON RGCs over OFF RGCs, mimicking a light response. The selective stimulation of ON RGCs and OFF RGCs was achievable in the degenerated retina, rd10. This shows that these stimulation pulses can be used to selectively target different RGCs with an implant on the RP retina. In this study, I have identified ways to generate electrical responses with greater efficiency and enhanced resolution in a degenerated retina. The implementation of these findings in afunctional implant would therefore improve the visual percepts elicited by an implant and thereby improve the quality of life for individuals with visual impairments.