Activation of retinal glial cells contributes to the degeneration of ganglion cells in experimental glaucoma

Yanying Miao; Guo-Li Zhao; Shuo Cheng; Zhongfeng Wang; Xiong-Li Yang

doi:10.1016/j.preteyeres.2023.101169

Activation of retinal glial cells contributes to the degeneration of ganglion cells in experimental glaucoma

Prog Retin Eye Res. 2023 Mar:93:101169. doi: 10.1016/j.preteyeres.2023.101169. Epub 2023 Feb 1.

Authors

Yanying Miao¹, Guo-Li Zhao¹, Shuo Cheng¹, Zhongfeng Wang², Xiong-Li Yang³

Affiliations

¹ State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China.
² State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. Electronic address: zfwang@fudan.edu.cn.
³ State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, 200032, China. Electronic address: xlyang@fudan.edu.cn.

PMID: 36736070
DOI: 10.1016/j.preteyeres.2023.101169

Abstract

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.

Keywords: Activation; Astrocyte; Glaucoma; Microglia; Müller cells; Retinal ganglion cell degeneration.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Glaucoma*
Gliosis* / pathology
Intraocular Pressure
Neuroglia / pathology
Retina / metabolism
Retinal Ganglion Cells / pathology