Cell division and cleavage orientation in the developing retina are regulated by L-DOPA

Recent studies have highlighted a potential link between the cleavage orientation of a dividing neuroblast and the regulation of daughter cell fate in the developing vertebrate retina. There is evidence to suggest that this process is at least partially regulated by the presence of the retinal pigment epithelium (RPE) and/or RPE-derived factors. In addition to a lack of melanin in the RPE, the albino retina is characterized by abnormal patterns of cell proliferation and cellular organization during development as well as cell-type specific deficits in the adult. We examined mitotic spindle orientation in vivo in developing pigmented and albino rat retinae along with other parameters of cell division to determine whether RPE abnormalities in the albino influence these aspects of retinal development. In the albino, mitotic indices were elevated, an excess of cells remained in the cell cycle, dividing cells were not so tightly apposed to the ventricular margin, and an excessive proportion of divisions was vertically oriented (i.e., with the mitotic spindle aligned perpendicular to the plane of the neuroepithelium). Administration of L-DOPA (a melanin precursor found at reduced concentrations in the hypopigmented eye) regulated the distribution of spindle orientations and reduced levels of mitosis in a manner consistent with an endogenous role in the control of these processes. These findings highlight the multiple roles that L-DOPA plays in the regulation of retinal development and cast light on the diversity of anatomical abnormalities found in the albino visual system. J. Comp. Neurol. 496:369-381, 2006. (c) 2006 Wiley-Liss, Inc.