Nickerson Philip E B, Emsley Jason G, Myers Tanya, Clarke David B
Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada.
Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5266-75. doi: 10.1167/iovs.07-0167.
Despite the identification of a small population of cells residing in the ciliary body (CB) of the adult mammalian eye that have the capacity to generate retina-like cells in vitro, their activity in vivo remains quiescent. The authors sought to identify whether the predictable and time-dependent death of retinal ganglion cells (RGCs) results in activation of progenitor-like cells within the CB.
RGC injury was induced by optic nerve axotomy in adult mice. Thymidine-analogue lineage tracing and immunocytochemistry were used to identify dividing cells and the phenotype of newly generated progeny.
Two populations of nestin-expressing cells are present in the CB of the uninjured eye. One population resides in periendothelial cells of blood vessels, and a second resides in the ciliary epithelium. Axotomy increases proliferation in the CB, a response that begins before the onset of RGC death and continues during a time that corresponds with the peak in RGC death. In addition, a subpopulation of nestin-positive cells in the CB upregulates the homeodomain protein Chx10. Finally, recoverin, the expression of which is normally restricted to photoreceptors and bipolar cells of the retina, is upregulated in the CB in a manner that is independent of proliferation.
Together, these results suggest that progenitorlike cells of the CB respond to cues associated with the loss of a single retinal cell type and that a subpopulation of those cells may differentiate into a cell that bears phenotypic resemblance to those seen in the retina.
尽管已发现成年哺乳动物眼睛睫状体(CB)中存在一小部分细胞,它们在体外具有生成视网膜样细胞的能力,但其在体内的活性仍处于静止状态。作者试图确定视网膜神经节细胞(RGCs)可预测的、随时间发生的死亡是否会导致CB内祖细胞样细胞的激活。
通过对成年小鼠进行视神经切断术诱导RGC损伤。使用胸腺嘧啶类似物谱系追踪和免疫细胞化学来鉴定分裂细胞和新生成子代的表型。
未受伤眼睛的CB中存在两类表达巢蛋白的细胞。一类位于血管的周内皮细胞中,另一类位于睫状体上皮中。视神经切断术会增加CB中的细胞增殖,这种反应在RGC死亡开始之前就已开始,并在与RGC死亡高峰期相对应的时间段内持续。此外,CB中巢蛋白阳性细胞的一个亚群上调了同源结构域蛋白Chx10。最后,恢复蛋白的表达通常仅限于视网膜的光感受器和双极细胞,它在CB中的上调方式与增殖无关。
总之,这些结果表明,CB中的祖细胞样细胞对与单一视网膜细胞类型丧失相关的信号有反应,并且这些细胞的一个亚群可能分化为与视网膜中所见细胞具有表型相似性的细胞。