Kwan, Anthony S. L.; (2003) Retinal transplantation in a rodent model of retinitis pigmentosa. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Over the past two decades, studies in rodents with photoreceptor degeneration have explored the use of retinal transplants to reconstruct the outer retina. More recently studies on transplantation have moved into human trials before any evidence of the functional inprovement of retinal transplants in animal experiments has been established. In the present work, I have pursued the possibility of using mechanically dissociated cells as donor material and have focused on three issues - the appearance of the graft itself, its interface with the host retina and the potential for functional restitution after transplantation. These studies have been conducted in an animal model of retinitis pigmentosa (RP), the retinal degeneration (rd) mouse, which is a direct homologue of one of the autosomal recessive forms of RP in humans. A technique was developed to transplant neonatal retinal microaggregates into the subretinal space of the mouse eye. The histology of the grafted eyes was examined and compared with normal and dystrophic mouse retinae without transplants. Different retinal cellular components were labelled with appropriate antibodies and the results showed that microaggregate transplants could produce a rod photoreceptor-rich cell layer. Evidence of host-graft connections was seen both in terms of synaptic protein labelling and in an increase in the number of synapses observed ultrastructurally. Such evidence was further supported by cross-species (rat to mouse) transplant experiments. Retinal graft function was assessed by light and dark preferential behaviour and measurement of retinal thresholds. Results were encouraging and showed some restoration of visual function following transplantation in a few animals but statistically not significant. It was a worthwhile investigation but results have to be interpreted with caution. Further investigation with a larger number of animals is recommended. This work has clinical relevance to the development of transplantation as a treatment for human retinal degeneration.

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