Effect of continuous electrical stimulation on retinal structure and function

Unrestricted Electrical stimulation of the central nervous system albeit an unnatural way, has been found to be an effective way of causing neuronal excitation. Retinal prosthesis is an example of such a neuroprosthesis that strives to provide vision to people suffering from Retinitis Pigmentosa and Age-related Macular Degeneration. In these diseases, the photoreceptors in the retina undergo a progressive degeneration leaving the remaining retinal neurons relatively intact. It is by electrically stimulating these retinal neurons that a retinal prosthesis aims to elicit visual percepts.; In addition to providing effective stimulation, such a device has to do so in a manner that is safe for both the device and surrounding biological environment. Numerous studies have been performed to assess the safety limits of electrical stimulation of neurons. However, majority of these studies have been performed in structures other than the retina. The few safety studies performed in the retina have looked at the effect of brief pulses of stimulation. Hence, the work presented in this thesis investigates the effect of prolonged stimulation of the retina on both the structure and function of the retina.; One-hour long epiretinal stimulation was performed in an in vivo animal model along with the recording of electrically evoked responses in the superior colliculus and retinal histology. Results presented in this thesis demonstrate that the retina is capable of tolerating continuous stimulation at charge densities higher than the safe limit of platinum even when delivered at high stimulus frequencies. However, such a stimulation regime causes a decrease in the electrically evoked responses in the superior colliculus resulting in an elevation of threshold of excitation. This temporary desensitization was found to occur within the first tens of seconds of stimulation after which the responses attained a steady state level. Observations made during this research points towards some form of adaptation by the retina in response to continuous electrical stimulation.; The work presented in this thesis is aimed towards the development of high-resolution epiretinal prosthesis. This research is one of the first to systematically investigate the effect of continuous stimulation from a safety perspective and will hopefully help in the design of safe and efficacious stimulus protocols for retinal prosthesis recipients.