Ophthalmology (Eye & Ear Hospital) - Theses
Permanent URI for this collection
Search Results
1 - 1 of 1
-
ItemBlind feline model for retinal prosthesis( 2015)Hereditary photoreceptor degenerations such as retinitis pigmentosa are a common and incurable cause of blindness in the western world. The development of visual prostheses that use electronic stimulation of the brain or retina to generate a visual percept is a novel field aimed at the restoration of functional vision in patients with photoreceptor degenerations. It is not well understood how changes in the visual pathway as a result of photoreceptor degeneration might impact the efficacy of an implanted visual prosthesis. In order to examine this relationship it is necessary to test the functioning of visual prostheses in a large eyed blind animal model. The aim of this study was to develop and characterise a blind feline model of photoreceptor degeneration using intravitreal injection of adenosine triphosphate (ATP), and to examine the effects of a chronic model of blindness on the efficacy of suprachoroidal electronic stimulation. In order to develop a blind model of photoreceptor degeneration we performed unilateral intravitreal injections of ATP in normal sighted cats. We assessed animals over a 12 week period post injection using electroretinography (ERG), optical coherence tomography (OCT) and retinal histology to determine a dose response and time course of retinal degeneration. Intravitreal injection of ATP lead to a rapid loss of rod photoreceptor function and a gradual loss of cone photoreceptor function within 12 weeks post ATP injection. The outer retina showed a progressive reduction in thickness over the 12 week assessment period, with the inner retina remaining intact. Our data shows that unilateral, intravitreal ATP injection can be used as a rapid, safe and effective model of photoreceptor degeneration in the feline. We examined the effect of ATP-induced retinal degeneration on the efficacy of a suprachoroidal prosthesis. At the conclusion of the previous experiment, four ATP-injected animals were anaesthetised and implanted with a suprachoroidal stimulating array in each eye. Cortical thresholds to stimulation were obtained with multi-unit recordings from the visual cortex. Suprachoroidal electrode thresholds were then correlated to histological markers of neural and glial thickness. ATP-induced retinal degeneration increased the charge threshold necessary to produce a cortical response to suprachoroidal stimulation. Higher thresholds correlated spatially to areas with increased gliotic activity within the retina. Our data suggests that neural and glial changes resulting from ATP induced photoreceptor degeneration influences the efficacy of electronic stimulation using a suprachoroidal prosthesis. Finally, we characterised the extent of neural and glial remodelling present within the retina 6 to 12 weeks following intravitreal ATP injection, using immunohistochemical markers for cell death, neural remodelling and gliosis. Ongoing photoreceptor cell death was present at 6 and 12 weeks after ATP injection. Retinal remodelling events including cell migration and aberrant neurite growth were present throughout retina at 12 weeks after ATP injection. Ganglion cell axons in the optic nerve appeared to remain intact. A thick glial scar containing no neural tissue was observed entombing the outer retina, which may help to explain the correlation between electrode threshold and glial thickness we had observed previously. Our data show that the ATP injected feline model of retinal degeneration undergoes secondary retinal degeneration and remodeling events similar to those commonly seen in other models of retinal degeneration. The primary outcome of this study was the development and characterisation of a feline model of photoreceptor degeneration. This new model has potential as a tool for the future development and optimisation of visual prostheses. We found that pathological gliosis as a result of ATP induced photoreceptor degeneration appeared to influence the efficacy of suprachoroidal electronic stimulation. This research can be used to further inform the optimisation of device placement and stimulation strategy for visual prostheses.