Retinal mitosis is regulated by dopa, a melanin precursor that may influence the time at which cells exit the cell cycle: analysis of patterns of cell production in pigmented and albino retinae.

A melanin-associated agent seems to play a role in regulating retinal development. When absent, diverse deficits occur. There is evidence that this agent regulates patterns of mitosis. This study examines retinal development in pigmented and albino rats to identify the regulating agent and its mode of action. Throughout neurogenesis, many more mitotic profiles are found in albinos than pigmented animals. At the peak of retinal neurogenesis, approximately 50% more mitotic profiles are found in albinos than in matched pigmented animals, resulting in abnormal retinal thickening. Concurrently, increasing numbers of pyknotic nuclei are identified, such that later in development retinal thickness normalises. However, the crude centre-to-periphery pattern of cell production is preserved. Abnormal cell proliferation is found in a range of albino rat strains, but it is not present in their brains, confirming that the abnormality is ocular and melanin related. Dopa is a critical element in initial stages of melanin synthesis and is present in abnormally low levels in developing albino retinae. Furthermore, it is an antimitotic agent. Addition of dopa to albino eyes in vitro normalises patterns of cell production. These results are consistent with the hypothesis that dopa is a major regulator of retinal cell production and that it influences the capacity of cells to exit the cell cycle.