Wang Jia-Wei, Chen Shi-Da, Zhang Xiu-Lan, Jonas Jost B
*State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, P.R. China †Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University, Heidelberg, Germany.
J Glaucoma. 2016 May;25(5):459-65. doi: 10.1097/IJG.0000000000000200.
To review the current research on microglia as it relates to glaucoma, and summarize the potential microglia-targeted therapies.
The data were collected from PubMed and Google Scholar databases published in English up to July 2014. Keywords used, both alone and in combination, in the database search included retinal microglia, over-activation and inhibition of microglia, and glaucoma.
Articles were selected and reviewed if they involved microglia in animal models or human patients with glaucoma. Moreover, we also cited some comprehensive amalgamation of published literature.
Together with the macroglia [astrocytes, ependymal cells, oligodendrocytes, radial (Müller) cells], the microglia form the supportive tissue of the central nervous system (CNS). Glial cells are generally smaller than the neural cells, but outnumber them by a factor of 5 to 10 with marked regional differences in the CNS. Approximately half of the volume of the CNS is composed of glial cells. Because of the blood-retina barrier, blood-born immunologic cells cannot penetrate into the retina under physiological conditions; the retinal microglial cells are the primary immunocompetent cells in the retina. The microglial cells are involved in any process of cell degeneration and loss, including retinal ganglion fiber and cell loss. Surveying the retinal tissue in normal situations as "spiders in a net," the retinal microglial cells change their form from a resting dendritic-like shape to an activated ameboid form in the case of invading microorganisms or cell damage. They are involved in the process of cell apoptosis and removal of the dead cells. Studies suggested that inhibition of the microglial cell activation in the case of optic nerve damage can increase the number of surviving retinal ganglion cells and may thus be neuroprotective.
Activated microglia appear early in the glaucomatous process and may contribute detrimentally to the neuronal apoptosis in the later stage. Neuroprotective strategies that inhibit activated microglia may provide novel treatment modalities for glaucomatous optic neuropathy and any other retinal and optic nerve disease.
回顾当前与青光眼相关的小胶质细胞研究,并总结潜在的以小胶质细胞为靶点的治疗方法。
数据收集自截至2014年7月以英文发表的PubMed和谷歌学术数据库。数据库搜索中单独或组合使用的关键词包括视网膜小胶质细胞、小胶质细胞的过度激活与抑制以及青光眼。
如果文章涉及青光眼动物模型或人类患者中的小胶质细胞,则对其进行选择和综述。此外,我们还引用了一些已发表文献的综合汇总。
小胶质细胞与大胶质细胞(星形胶质细胞、室管膜细胞、少突胶质细胞、放射状[米勒]细胞)共同构成中枢神经系统(CNS)的支持组织。胶质细胞通常比神经细胞小,但在CNS中数量比神经细胞多5至10倍,且存在明显的区域差异。CNS约一半的体积由胶质细胞组成。由于血视网膜屏障,在生理条件下血源性免疫细胞无法穿透进入视网膜;视网膜小胶质细胞是视网膜中的主要免疫活性细胞。小胶质细胞参与任何细胞变性和丢失的过程,包括视网膜神经节纤维和细胞的丢失。在正常情况下,视网膜小胶质细胞像“网中的蜘蛛”一样审视视网膜组织,在入侵微生物或细胞损伤时,它们会从静止的树突状形态转变为活化的阿米巴样形态。它们参与细胞凋亡过程以及死细胞的清除。研究表明,在视神经损伤时抑制小胶质细胞的激活可增加存活的视网膜神经节细胞数量,因此可能具有神经保护作用。
活化的小胶质细胞在青光眼病程早期出现,可能在后期对神经元凋亡产生有害影响。抑制活化小胶质细胞的神经保护策略可能为青光眼性视神经病变以及任何其他视网膜和视神经疾病提供新的治疗方式。