眼内压升高（IOP）是青光眼神经退行性的主要风险因素。胶质细胞在正常视网膜神经元功能中起着重要的作用，在实验性青光眼动物模型中，这些细胞被广泛涉及到视网膜节细胞（RGC）的退化中。在应对升高的IOP时，首先启动的是mGluR I，然后是Kir4.1通道的抑制，这导致了密勒细胞的激活。密勒细胞的激活随后接着一个复杂的过程，包括增殖、释放炎性和生长因子（胶质瘤）。这种胶质化进一步受到多种因素的调节。激活的密勒细胞通过产生谷氨酸受体介导的兴奋性毒性、释放细胞毒性因子和诱导小胶质细胞激活，有助于RGC的退化。升高的IOP激活微胶质细胞，并随着形态和功能的改变，这些细胞作为视网膜的居民免疫细胞，展现出增强的自适应免疫反应，包括释放促炎症因子（肿瘤神经元因子α、白细胞介素等）。这些ATP和Toll样受体介导的反应受到热休克蛋白、CD200R、趋化因子受体和代谢型嘌呤能受体的进一步调节，可能加重RGC的损失。在视神经头部，星形胶质化是通过嘌呤、递质、趋化因子、生长因子和细胞因子的复杂反应过程启动和调节的，这些分子通过释放促炎症因子和改变青光眼中的细胞外基质来造成RGC轴突损伤。激活的胶质细胞对RGC的影响受到不同类型胶质细胞之间相互作用的影响。本文最后提出了这个领域未来可能的研究方向。版权所有 © 2023 Elsevier Ltd.

Elevation of intraocular pressure (IOP) is a major risk factor for neurodegeneration in glaucoma. Glial cells, which play an important role in normal functioning of retinal neurons, are well involved into retinal ganglion cell (RGC) degeneration in experimental glaucoma animal models generated by elevated IOP. In response to elevated IOP, mGluR I is first activated and Kir4.1 channels are subsequently inhibited, which leads to the activation of Müller cells. Müller cell activation is followed by a complex process, including proliferation, release of inflammatory and growth factors (gliosis). Gliosis is further regulated by several factors. Activated Müller cells contribute to RGC degeneration through generating glutamate receptor-mediated excitotoxicity, releasing cytotoxic factors and inducing microglia activation. Elevated IOP activates microglia, and following morphological and functional changes, these cells, as resident immune cells in the retina, show adaptive immune responses, including an enhanced release of pro-inflammatory factors (tumor neurosis factor-α, interleukins, etc.). These ATP and Toll-like receptor-mediated responses are further regulated by heat shock proteins, CD200R, chemokine receptors, and metabotropic purinergic receptors, may aggravate RGC loss. In the optic nerve head, astrogliosis is initiated and regulated by a complex reaction process, including purines, transmitters, chemokines, growth factors and cytokines, which contributes to RGC axon injury through releasing pro-inflammatory factors and changing extracellular matrix in glaucoma. The effects of activated glial cells on RGCs are further modified by the interplay among different types of glial cells. This review is concluded by presenting an in-depth discussion of possible research directions in this field in the future.Copyright © 2023 Elsevier Ltd. All rights reserved.