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Purpose <p>Glaucoma is an optic neuropathy characterized by progressive death of retinal ganglion cells (RGCs), ultimately leading to blindness. Increasing evidence demonstrates that interactions among retinal glial cells exacerbate retinal inflammatory responses, which is closely associated with RGC injury. However, the detailed mechanisms governing these glial cell interactions remain largely unknown. This study aims to investigate the possible roles and the potential mechanisms of interleukin-1β (IL-1β) in mediating the interaction between Müller cells and microglia in glaucoma.</p> Methods <p>The experimental glaucoma model of chronic ocular hypertension (COH) was established in adult male mice by injection of micro-magnetic beads into the anterior chamber. Western blotting, quantitative real-time polymerase chain reaction, immunofluorescence, transwell co-culture of glial cells, RNA sequence, swept-source optical coherence tomography-based imaging and flash visually evoked potentials were employed to investigate the underlying mechanisms about the interaction of Müller cells and microglia in retina after IL-1β stimulation, along with their impact on visual functions.</p> Results <p>We showed that in COH retinas, IL-1β activated Müller cells and microglia, and promoted the recruitment of microglia to the ganglion cell layer. Mechanistic studies revealed that activated Müller cells released C-X-C motif chemokine ligand 1/5 (CXCL1/5) through the NF-κB and p38 MAPK signaling pathways. These chemokines bond to CXC chemokine receptor 2 (CXCR2), inducing microglial activation and migration. This activation led to a significant increase in the expression of pro-inflammatory factors, which contributed to RGC death and subsequent visual function decline. Importantly, inhibition of the CXCL1/5-CXCR2 axis substantially reversed RGC loss and improved visual function.</p> Conclusions <p>IL-1β plays a positive feedback role in glial cell interactions, amplifying retinal inflammatory responses and impairing visual function. These findings demonstrate that inhibiting the interaction between Müller cells and microglia effectively protects RGCs, offering a promising strategic approach for glaucoma prevention and treatment.</p> Graphical Abstract <p></p>

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IL-1β-mediated interaction between Müller cells and microglia through CXCL1/5-CXCR2 aggravates visual dysfunction in experimental glaucoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Xiaoyu Xin,
  • Luying Han,
  • Yuntao Qu,
  • Lujia Zhang,
  • Xiaoli Zhang,
  • Jiarui Li,
  • Bo Lei,
  • Yong-Chen Wang,
  • Zhongfeng Wang

摘要

Purpose

Glaucoma is an optic neuropathy characterized by progressive death of retinal ganglion cells (RGCs), ultimately leading to blindness. Increasing evidence demonstrates that interactions among retinal glial cells exacerbate retinal inflammatory responses, which is closely associated with RGC injury. However, the detailed mechanisms governing these glial cell interactions remain largely unknown. This study aims to investigate the possible roles and the potential mechanisms of interleukin-1β (IL-1β) in mediating the interaction between Müller cells and microglia in glaucoma.

Methods

The experimental glaucoma model of chronic ocular hypertension (COH) was established in adult male mice by injection of micro-magnetic beads into the anterior chamber. Western blotting, quantitative real-time polymerase chain reaction, immunofluorescence, transwell co-culture of glial cells, RNA sequence, swept-source optical coherence tomography-based imaging and flash visually evoked potentials were employed to investigate the underlying mechanisms about the interaction of Müller cells and microglia in retina after IL-1β stimulation, along with their impact on visual functions.

Results

We showed that in COH retinas, IL-1β activated Müller cells and microglia, and promoted the recruitment of microglia to the ganglion cell layer. Mechanistic studies revealed that activated Müller cells released C-X-C motif chemokine ligand 1/5 (CXCL1/5) through the NF-κB and p38 MAPK signaling pathways. These chemokines bond to CXC chemokine receptor 2 (CXCR2), inducing microglial activation and migration. This activation led to a significant increase in the expression of pro-inflammatory factors, which contributed to RGC death and subsequent visual function decline. Importantly, inhibition of the CXCL1/5-CXCR2 axis substantially reversed RGC loss and improved visual function.

Conclusions

IL-1β plays a positive feedback role in glial cell interactions, amplifying retinal inflammatory responses and impairing visual function. These findings demonstrate that inhibiting the interaction between Müller cells and microglia effectively protects RGCs, offering a promising strategic approach for glaucoma prevention and treatment.

Graphical Abstract