Xue L P, Lu J, Cao Q, Hu S, Ding P, Ling E-A
Department of Anatomy, Yong Loo Lin School of Medicine, Block MD 10, 4 Medical Drive, National University of Singapore, Singapore 117597.
Neuroscience. 2006 May 12;139(2):723-32. doi: 10.1016/j.neuroscience.2005.12.032. Epub 2006 Feb 3.
This study was aimed to investigate reactive changes of Müller glial cells in rats subjected to experimentally induced glaucoma. In the latter, it is well documented that elevated intraocular pressure leads to the loss of ganglion cells as confirmed in this study. The present results have shown that Müller glial cells as well as astrocytes closely associated with the ganglion cells reacted vigorously to increased intraocular pressure as manifested by the induced and upregulated expression of nestin and glial fibrillar acidic protein. A major finding in glaucomatous rats was the induced expression of nestin together with glial fibrillar acidic protein with the rise of the intraocular pressure beginning at 2 h. The marked nestin expression appeared to be most intense at 1 week after operation and was sustained at 3 weeks. Induced nestin expression in Müller glial cells was demonstrated unequivocally in whole-mount preparation of the retina. In the same tissue preparation, nestin expression was also detected in some astrocytes. Western blotting analysis confirmed a marked increase in expression of nestin and glial fibrillar acidic protein. Present results suggest that nestin as well as glial fibrillar acidic protein is a useful biomarker for retina injury. The induced expression of these intermediate filament proteins in Müller glial cells especially at their end-feet and also in some astrocytes adjoining the neuronal injury suggests a potential neuroprotective mechanism in response to acute rise in intraocular pressure resulting in neuronal degeneration.
本研究旨在探讨实验性诱导青光眼大鼠 Müller 胶质细胞的反应性变化。在后者中,已有充分文献证明眼内压升高会导致神经节细胞丢失,本研究也证实了这一点。目前的结果表明,Müller 胶质细胞以及与神经节细胞密切相关的星形胶质细胞对眼内压升高反应强烈,表现为巢蛋白和胶质纤维酸性蛋白的诱导表达上调。青光眼大鼠的一个主要发现是,随着眼内压在 2 小时开始升高,巢蛋白与胶质纤维酸性蛋白一起被诱导表达。显著的巢蛋白表达在术后 1 周似乎最为强烈,并在 3 周时持续存在。在视网膜整装标本中明确证实了 Müller 胶质细胞中巢蛋白的诱导表达。在相同的组织标本中,也在一些星形胶质细胞中检测到了巢蛋白表达。蛋白质印迹分析证实巢蛋白和胶质纤维酸性蛋白的表达显著增加。目前的结果表明,巢蛋白以及胶质纤维酸性蛋白是视网膜损伤的有用生物标志物。这些中间丝蛋白在 Müller 胶质细胞尤其是其终足以及一些毗邻神经元损伤的星形胶质细胞中的诱导表达,提示了一种针对因眼内压急性升高导致神经元变性的潜在神经保护机制。