Activation of neural progenitor cells in human eyes with proliferative vitreoretinopathy
Activation of neural progenitor cells in human eyes with proliferative vitreoretinopathy
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DOI：
10.1016/j.exer.2012.03.008
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发表时间：
2012-05-01
影响因子：
3.4
通讯作者：
Moe, Morten C.
中科院分区：
文献类型：
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作者：
Johnsen, Erik O.;Froen, Rebecca C.;Moe, Morten C.
神经干/祖细胞（neural stem/progenitor cells，NSCs）除了具有自我更新和功能分化的能力外，还可以通过靶向迁移对CNS损伤做出反应。在低等脊椎动物中，已知视网膜损伤激活睫状边缘区（CMZ）中的NSC。表达NSC标志物的细胞也存在于成年人眼睛的周边视网膜（PR）中的睫状体上皮（CE）和Muller神经胶质中。然而，这些细胞在成年人眼中似乎处于静止状态，最近的报告表明CE细胞具有NSC的有限特性。为了进一步阐明成年人眼中是否存在神经干细胞，我们测试了在患有增生性玻璃体视网膜病变（PVR）的眼睛中是否可以激活神经干细胞样细胞。在人类摘除的对照眼和患有确认的PVR的眼以及PVR的小鼠模型中，研究了PR和CE的NSC-associated标志物。此外，将从用于视网膜脱离的玻璃体切除术期间获得的玻璃体样品中分离的细胞直接固定或在干细胞促进培养基中培养，并与从死后视网膜和CE培养的细胞进行比较。正常眼睛的原位表征揭示了仅在近端平坦部区域和PR的外周囊肿周围的NSC中存在的标记物（巢蛋白、Sox 2、Pax 6）的稳健表达，后者群体还对胶质细胞标记物GFAP染色。虽然PVR眼CE中分裂细胞的数量高于对照组，但我们在CE中未检测到NSC-associated标志物，除了近端扁平部囊肿周围。在PVR小鼠眼内，CE中也发现Nestin活化。在人类PVR眼中，非神经胶质细胞和神经胶质细胞共染色神经干细胞相关标志物的增殖是明显的锯齿缘周围区域。与来自没有已知PVR的患者的2/15个样品相比，来自PVR患者的7/10个玻璃体样品中形成球体，并且在直接固定和重复传代后均表达胶质细胞和神经干细胞相关标志物。总之，成年人的眼睛可能窝藏两个不同的群体的神经上皮干细胞/祖细胞;非胶质细胞的人口位于近端睫状体平坦部周围的周边囊肿，除了人口与穆勒神经胶质细胞的特点。然而，我们只发现神经胶质细胞群体能够通过靶向迁移到玻璃体中来对视网膜损伤做出反应。(c)2012爱思唯尔有限公司保留所有权利。
In addition to the ability for self-renewal and functional differentiation, neural stem/progenitor cells (NSCs) can respond to CNS injuries by targeted migration. In lower vertebrates, retinal injury is known to activate NSCs in the ciliary marginal zone (CMZ). Cells expressing markers of NSCs are also present in the ciliary body epithelium (CE) and in Muller glia in the peripheral retina (PR) of the adult human eye. However, these cells seem to be quiescent in the adult human eye and recent reports have shown that CE cells have limited properties of NSCs. In order to further clarify whether NSCs exist in the adult human eye, we tested whether NSC-like cells could be activated in eyes with proliferative vitreoretinopathy (PVR). The PR and CE were studied for NSC-associated markers in human enucleated control eyes and eyes with confirmed PVR, as well as in a mouse model of PVR. Furthermore, cells isolated from vitreous samples obtained during vitrectomies for retinal detachment were directly fixed or cultured in a stem cell-promoting medium and compared to cells cultured from the post-mortem retina and CE. In situ characterization of the normal eyes revealed robust expression of markers present in NSCs (Nestin, Sox2, Pax6) only around peripheral cysts of the proximal pars plana region and the PR, the latter population also staining for the glial marker GFAP. Although there were higher numbers of dividing cells in the CE of PVR eyes than in controls, we did not detect NSC-associated markers in the CE except around the proximal pars plana cysts. In the mice PVR eyes, Nestin activation was also found in the CE. In human PVR eyes, proliferation of both non-glial and glial cells co-staining NSC-associated markers was evident around the ora serrata region. Spheres formed in 7/10 vitreous samples from patients with PVR compared to 2/15 samples from patients with no known PVR, and expressed glial - and NSC-associated markers both after direct fixation and repetitive passages. In conclusion, the adult human eye may harbor two different populations of neuroepithelial stem/progenitor cells; a non-glial population located in the proximal pars plana around peripheral cysts in addition to a population with Muller glia characteristics. Yet, we only found that the glial population was able to respond to retinal injury by targeted migration into the vitreous. (c) 2012 Elsevier Ltd. All rights reserved.