Ilia, Maria; (1998) Melanin: its role in retinal development. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Melanin related agents influence retinal development. In albinos the normal centre to periphery pattern of retinal maturation is delayed and there are diverse retinal deficits at maturity. There is evidence that the abnormality may arise from a disruption in the pace of retinal development, as in albinos the normal centre to periphery pattern of retinal maturation is either disrupted or delayed. This study examines the hypothesis that a melanin related agent, probably dopa, influences the time at which cells leave the cell cycle. Throughout neurogenesis levels of mitosis were higher in albinos than in pigmented animals. This difference was consistent between various albino and pigmented strains. There were no differences in mitotic numbers in their brains. Excess mitosis resulted in retinal thickening followed by a period of excess cell death which reduced cell numbers. There were no differences in the spatio-temporal patterns of these events between the animals. Tyrosinase triggers melanin synthesis by catalysing dopa production from tyrosine. Retinal dopa levels were measured with HPLC and found to be reduced by -30% in developing albinos. Dopa is an anti-mitotic agent and its application in vitro slows RPE cell cycle rates. Could reduced dopa result in excess mitosis. Developing eyes from both strains were maintained in organ culture with or without dopa for 7h. Without dopa mitosis was similar to that found in vivo. However, addition of the drug at appropriate doses reduced the mitotic profiles in albino retinae but had no significant effect on pigmented eyes. These results are consistent with the notion that a melanin related agent, probably dopa, acts as a break on mitosis in the developing retina. Perhaps its influence regulates the pace of retinal development.

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