Delayed neurogenesis in the albino retina: evidence of a role for melanin in regulating the pace of cell generation.

Melanin or an associated product in the retinal pigment epithelium (RPE) regulates retinal maturation, because in albino mammals the central retina is underdeveloped and there is a cell specific deficit in the rod population. Further, retinal projections through the chiasm are disrupted systematically. Here we test the hypothesis that melanin influences the birth dates of cells in the ganglion cell layer of the rat. [3H]Thymidine was injected at stages between E12 and E21 into mothers carrying both pigmented and albino fetuses. The animals were examined at maturity. Both pigmentation genotypes showed a centre to periphery pattern of cell production. Injections at E12 resulted in similar patterns of labelling in central regions. But from E14 labelled cells in the albinos were consistently closer to the central retina than those in their pigmented litter mates, suggesting a temporal lag in the centre to periphery pattern of cell production. By E21 there was little or no label in the pigmented animals, but it persisted in albinos, being similar in distribution to that in pigmented animals injected at E19. These results are consistent with the notion that melanin, or more likely an affiliated agent, in the RPE plays a role in regulating mitosis in the neural retina, possibly by influencing an aspect of the cell cycle. This may be the origin of the abnormalities found in the adult.