> Publications > Tumor Necrosis Factor Alpha-Mediated Interaction Between Microglia and Müller Cells Exacerbates Retinal Ganglion Cell Damage in Experimental Glaucoma

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Publication

April 3, 2026 • ✎ STRIA TECH

Tumor Necrosis Factor Alpha-Mediated Interaction Between Microglia and Müller Cells Exacerbates Retinal Ganglion Cell Damage in Experimental Glaucoma

Topics:

Glaucoma

Glaucoma and Optic Nerve Neurodegeneration

Neuroinflammation

Neuroinflammation and Autoimmune CNS Disease

Optic Nerve Damage

Retinal Degeneration and Inherited Retinal Disease

Retinal Ganglion Cell Pathology

Publication

Neuroscience Bulletin (Aug 30, 2025) Tumor Necrosis Factor Alpha-Mediated Interaction Between Microglia and Müller Cells Exacerbates Retinal Ganglion Cell Damage in Experimental Glaucoma

Li SY, Zhou H, Zhao G, Ding WW, Zhang Y, Wang YC, Li F, Miao Y, Sun XH, Wang Z

DOI: 10.1007/s12264-025-01478-1 >>

In glaucoma, retinal ganglion cell death is mediated by neuroinflammation which in turn is aggravated by interactions between Müller glia and microglia. Li et al. investigated the role of tumor necrosis factor-alpha (TNF-α, produced by activated microglia) in the crosstalk between micro- and Müller glia. In a chronic ocular hypertension (COH) glaucoma model, elevated TNF-α activated both Müller cells and microglia, promoted microglial recruitment to the ganglion cell layer, and amplified neuroinflammation and RGC injury.

Interaction between Müller cells and microglia aggravates neuroinflammation, resulting in retinal ganglion cell (RGC) death in glaucoma. Here, we investigated how tumor necrosis factor-alpha (TNF-α) produced by activated microglia mediates the crosstalk between Müller cells and microglia and impacts RGC injury in a chronic ocular hypertension (COH) glaucoma model. In COH retinas, elevated TNF-α induced the activation of Müller cells and microglia, and recruited microglia to the ganglion cell layer. Co-culture with Müller cells enhanced TNF-α-induced microglial activation, migration, and proliferation. Both in vivo and in vitro experiments confirmed that chemokine C-C motif ligand 2 (CCL2), primarily released from Müller cells, mediated the TNF-α-induced effects on microglia in COH retinas. Knockdown of CCL2 attenuated RGC damage and vision loss. Our results demonstrate that TNF-α released from microglia induces the secretion of CCL2 from Müller cells, thus inducing microglial activation and migration, exacerbating retinal neuroinflammation and RGC injury in glaucoma.