Regulation of immunological equilibrium by IL-6/STAT3 in glaucomatous irises and its effect on filtering bleb success

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PURPOSE: To investigate the expression of interleukin-6 (IL-6) and its associated downstream genes within iris tissues of primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and secondary glaucoma (neovascular, traumatic, and uveitic) subjects, assess cytokines correlation and their influence on trabeculectomy success. METHODS: This prospective single-center study analyzed IL-6 and its downstream signaling molecules expression levels by real-time polymerase chain reaction (RT-PCR) that consisted of 25 glaucoma eyes (POAG: 10, PACG: 8, secondary glaucoma: 7) and nine eyes from the corneoscleral rims that served as controls. Correlation matrices assessed the association between these factors and trabeculectomy outcomes. RESULTS: Compared to controls, a significant downregulation of IL-6 expression (Control vs. POAG P = 0.004, Control vs. PACG P = 0.002); IL-6R (Control vs. POAG P = 0.0002, Control vs. PACG P = 0.012); gp130 (Control vs. POAG P = 0.003) was observed in primary glaucoma. Also, differential expression of apoptosis markers BAX (Control vs. POAG P = 0.043); BCL-2 (Control vs. POAG P = 0.002, Control vs. PACG P = 0.007), and fibrotic markers α-SMA (Control vs. POAG P = 0.01, Control vs. PACG P = 0.04) was observed. Similar cytokine expressions were observed in secondary glaucoma compared to the controls. The overall success rate of trabeculectomy was 94.11% at three months postoperatively. A significant correlation was found between IL-6R and its downstream targets. CONCLUSION: These findings suggested that in glaucomatous irises, altered IL-6/STAT3 signaling indicates a balance between pro- and anti-inflammatory factors, potentially explaining trabeculectomy's early effectiveness via this immunological balance.

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