Lee, E.J.K.; (2012) Cone photoreceptor neuroprotection in inherited retinal degenerations. Doctoral thesis , UCL (University College London).

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Abstract

High resolution and colour vision is derived from cone photoreceptors within the retina of the eye. These highly specialised neuronal cells convert energy from incident light into changes in cellular membrane potential. Action potentials are then relayed and processed within the inner retina and the cerebral cortex. Loss of function in the cone photoreceptors is the direct cause of visual loss for millions o f patients. Yet for many of the most common causes of blindness cone photoreceptor dysfunction occurs late on in the disease and is secondary to inherited and/or environmental influences that primarily affect other cell types. Cone photoreceptors are then secondarily affected and it is once their function is lost that the patient becomes visually disabled. The aim of this thesis was to evaluate therapies targeting the molecular steps of cone photoreceptor death rather than the underlying pathology. If effective at slowing cone photoreceptor degeneration and preserving function, such therapies could be applicable to large numbers of patients with a variety of underlying defects. There will however be continued stimuli for cell death as the primary defect has not been corrected and so it is important to determine the magnitude and duration of any treatment effect. The experiments of this thesis were performed in an animal model of inherited retinal degeneration derived to allow repeated in vivo assessments of cone photoreceptor function and survival. Gene therapy and intra-ocular injections were used to evaluate proteins with contrasting modes of action.

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