Wohl Stefanie G, Schmeer Christian W, Kretz Alexandra, Witte Otto W, Isenmann Stefan
Department of Experimental Neurology, University of Jena Medical School, Erlanger Allee 101, 07747 Jena, Germany.
Exp Neurol. 2009 Sep;219(1):175-86. doi: 10.1016/j.expneurol.2009.05.008. Epub 2009 May 13.
In the naïve adult rodent eye cell proliferation does not occur. The aim of this in vivo study was to evaluate if quiescent putative progenitor-like cells within the adult mouse eye can be activated by optic nerve (ON) injury. For a comprehensive analysis, three areas were assessed: the ON, the neural retina, and the ciliary body (CB). Two lesion types were performed, i.e. intraorbital ON transection, or ON crush lesion, in order to analyse possible differences in cellular response after injury. This mouse study shows, for the first time that ON lesion up-regulates cell proliferation and nestin expression in the mouse eye as compared to naïve controls. Numbers and distribution patterns of BrdU+ cells obtained were similar after both lesion types, suggesting analogous mechanisms of activation. Interestingly, a differential cell proliferative response was observed in the CB. After ON lesion, the absence of BrdU/TUNEL co-labelled cells confirmed that BrdU+ cells were indeed proliferating. Following ON lesion, in the retina approximately 18% of all BrdU+ cells were positive for the neural stem cell/progenitor cell (NSC/PC) marker nestin. The fraction of BrdU+/nestin+ cells in the CB was approximately 26%. Most of the BrdU+/nestin+ cells found in the neural retina were identified as reactive astrocytes and Müller cells. Since reactive glia cells can participate in adult neuro- and gliogenesis this may indicate a potential for regeneration after ON lesion in vivo.
在未受损伤的成年啮齿动物眼中，细胞增殖不会发生。本体内研究的目的是评估成年小鼠眼内静止的假定祖细胞样细胞是否能被视神经（ON）损伤激活。为了进行全面分析，评估了三个区域：视神经、神经视网膜和睫状体（CB）。进行了两种损伤类型，即眶内视神经横断或视神经挤压损伤，以分析损伤后细胞反应的可能差异。这项小鼠研究首次表明，与未受损伤的对照组相比，视神经损伤上调了小鼠眼中的细胞增殖和巢蛋白表达。两种损伤类型后获得的BrdU+细胞数量和分布模式相似，表明激活机制类似。有趣的是，在睫状体中观察到了不同的细胞增殖反应。视神经损伤后，BrdU/TUNEL共标记细胞的缺失证实了BrdU+细胞确实在增殖。视神经损伤后，在视网膜中，所有BrdU+细胞中约18%对神经干细胞/祖细胞（NSC/PC）标记物巢蛋白呈阳性。睫状体中BrdU+/巢蛋白+细胞的比例约为26%。在神经视网膜中发现的大多数BrdU+/巢蛋白+细胞被鉴定为反应性星形胶质细胞和穆勒细胞。由于反应性胶质细胞可参与成体神经发生和胶质生成，这可能表明体内视神经损伤后具有再生潜力。
