REVIEW article
Front. Immunol.
Sec. Systems Immunology
Glial-Mediated Immune Modulation in Glaucomatous Neurodegeneration: Mechanisms and Therapeutic Implications
Provisionally accepted
- Second Affiliated Hospital of Jilin University, Changchun, China
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Glaucoma, a leading cause of irreversible blindness, is characterized by retinal ganglion cell (RGC) degeneration and optic nerve damage. While elevated intraocular pressure (IOP) is a major risk factor, emerging evidence highlights neuroinflammation as a critical driver of disease progression. Glial cells, particularly microglia, astrocytes, and Müller cells, are central to this inflammatory process, orchestrating immune responses through the release of cytokines, chemokines, and complement proteins. Microglia and astrocytes contribute to early inflammatory amplification through tumor necrosis factor-alpha (TNF-α), complement, and Toll-like receptor 4 (TLR4) pathways, while Müller cells further promote tissue damage via ATP/P2X7R signaling and senescence-associated mechanisms. Leukocyte infiltration, triggered by glial-derived chemokines and matrix metalloproteinases (MMPs), underscores the intersection of innate and adaptive immunity in glaucoma. Importantly, preclinical studies demonstrate that targeting neuroinflammatory pathways confers RGC protection, thus modulating glial activation and immune signaling represents a promising therapeutic strategy for glaucoma, particularly in IOP-refractory cases. This review synthesizes current knowledge on the role of glial cells in initiating and perpetuating immune responses that exacerbate RGC loss, and details how activated microglia and astrocytes release pro-inflammatory mediators and upregulate pathogenic signaling pathways.
Keywords: Glaucoma, Neuroinflammation, Microglia, Astrocytes, Müller cells, TNF-α, complement, TLR4
Received: 03 Jun 2025; Accepted: 13 Nov 2025.
Copyright: © 2025 Zong, You, Hong and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Fangwei Zong, shomaru313@jlu.edu.cn
Wu Hong, wu_hong@jlu.edu.cn
Xuerui Wang, wangxuerui1314@jlu.edu.cn
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