Retinal cell addition and rod production depend on early stages of ocular melanin synthesis

Abstract

Retinal mitosis is regulated by dopa, a melanin precursor present in the developing retinal pigment epithelium. Its absence results in retinal deficits including a failure of approximately 30% of the rod population to develop. Here, (3)H-thymidine labelling is used to analyse patterns of cell addition spanning the main period of retinal development in rat litters containing both pigmented and albino phenotypes. Many more thymidine-labelled cells are found in each cellular layer at maturity in albinos than in their pigmented littermates. Normal spatial patterns of photoreceptor addition are seen in albinos during cone production and for most of the subsequent period of rod addition. However, abnormal spatial patterns of cell addition occur across the retinal when rod production peaks. A delay in the centre to periphery gradient of cell addition is apparent in both nuclear layers. These data are related to deficits in the mature architecture of the albino retina. The results are consistent with there being significant cell cycle and/or exit point irregularities in hypopigmented retinae. It is probable that reduced dopa levels in albinos result in the cell cycle rate not slowing appropriately with development, which may lead to cells missing their exit points. This produces abnormal patterns of cell addition at key stages and delays in the gradient of retinal maturation along with a large cell loss at critical stages of rod production.