Tibber Marc S, Whitmore Alan V, Jeffery Glen
Institute of Ophthalmology, University College London, UK.
J Comp Neurol. 2006 May 20;496(3):369-81. doi: 10.1002/cne.20920.
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.
最近的研究突出了发育中的脊椎动物视网膜中，分裂的神经母细胞的分裂方向与子细胞命运调控之间的潜在联系。有证据表明，这一过程至少部分受视网膜色素上皮（RPE）和/或RPE衍生因子的存在调控。除了RPE中缺乏黑色素外，白化病视网膜的特征还包括发育过程中细胞增殖和细胞组织的异常模式，以及成年期细胞类型特异性缺陷。我们研究了发育中的有色和白化病大鼠视网膜中体内有丝分裂纺锤体的方向以及细胞分裂的其他参数，以确定白化病中RPE的异常是否会影响视网膜发育的这些方面。在白化病大鼠中，有丝分裂指数升高，过多细胞停留在细胞周期中，分裂细胞与脑室边缘的贴附不紧密，并且过多比例的分裂是垂直方向的（即有丝分裂纺锤体与神经上皮平面垂直排列）。给予L - DOPA（在色素减退眼中浓度降低的黑色素前体）以一种与这些过程控制中的内源性作用一致的方式调节纺锤体方向的分布并降低有丝分裂水平。这些发现突出了L - DOPA在视网膜发育调控中所起的多种作用，并揭示了白化病视觉系统中发现的解剖学异常的多样性。《比较神经学杂志》496:369 - 381, 2006。(c) 2006威利 - 利斯公司。
