Tibber, Marc Samuel; (2004) Developmental abnormalities associated with the hypopigmented retina. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The albino visual system is characterised by a range of abnormalities including a severe rod deficit, an underdevelopment of the central retina and a misprojection of a portion of the temporal ganglion cells. During development of the retina levels of proliferation and apoptosis are elevated, and the maturational gradient is delayed. There is evidence from in vitro studies to suggest that L-DOPA, a precursor in both the melanin and catecholamine synthesis pathways, is able to regulate these abnormal patterns of cell proliferation in a manner which is consistent with its role in the regulation of retinal development. The aims of this thesis were; (1) to further characterise the developmental abnormalities associated with albinism, (2) to examine the effects of L-DOPA on patterns of cell division and neurogenesis within an in vivo context, and (3) to determine the mechanisms by which L-DOPA mediates its effects. Using both in vivo and in vitro methods, patterns of cell division and retinal differentiation were examined in pigmented and albino rat tissue. Results demonstrate that coincidental with abnormal levels of proliferation, the early postnatal albino retina is characterised by; a thickening of the neuroblastic layer, an excess of cells in the cell cycle, defects in the distribution of cleavage orientations within the apical-basal plane and elevations in gap junction expression. Furthermore, the vast majority of these parameters could be regulated by the introduction of L-DOPA to the retina and -preliminary experiments would suggest- through the addition of dopamine. These findings are consistent with a model in which reduced levels of L-DOPA in the albino retina lead to spatiotemporal defects in patterns of cell division, potentially as a result of secondary consequences on concentrations of retinal dopamine.

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