Neutrophil Extracellular Trap Components Are Present in the Aqueous Humor of Glaucoma Patients.

PURPOSE

The purpose of this study was to determine whether neutrophil extracellular trap (NET)-related markers are elevated in the aqueous humor of patients with glaucoma compared with healthy controls.

METHODS

We performed a case-control study of patients scheduled to undergo cataract extraction and/or glaucoma surgery from 2020 to 2022.

RESULTS

One hundred seventy-seven eyes were included: 127 were healthy controls, 43 were patients with glaucoma, and 7 were patients with uveitis. Pro-inflammatory markers were elevated in glaucomatous aqueous humor as compared with controls including: interleukin-1β (IL-1β; 1.31 pg/mL, interquartile range [IQR] = 1.87 vs. 1.12 pg/mL, IQR = 0.55, P < 0.0001), interferon gamma-inducible protein 10 (IP-10; 61.4 pg/mL, IQR = 106 vs. 25.9 pg/mL, IQR = 36.4, P = 0.0002), IL-8 (5.46 pg/mL, IQR = 5.10 vs. 2.52 pg/mL, IQR = 2.16, P < 0.0001), neutrophil gelatinase-associated lipocalin (NGAL; 2760 pg/mL, IQR = 4450 vs. 1690 pg/mL, IQR = 1370, P < 0.0001), and eDNA (0.0324 µg/mL, IQR = 0.0400 vs. 0.025 µg/mL, IQR = 0.0120, P < 0.0001). Furthermore, the glaucoma group had higher levels of IgG (3470 ng/mL, IQR = 4130 vs. 2370 ng/mL, IQR = 1800, P < 0.0001), IgA (188 ng/mL, IQR = 315 vs. 84.9 ng/mL, IQR = 198, P = 0.001), and IgM (3.45 ng/mL, IQR = 2.32 vs. 3.00 ng/mL, IQR = 0.880, P = 0.033) within the aqueous humor than the controls.

CONCLUSIONS

Multiple levels of the inflammatory pathway are implicated in glaucoma, including inflammatory cytokines (IL-1β), T-cell mediators (IP-10), neutrophil chemoattractant (IL-8), NET-associated molecules (NGAL and eDNA), and the adaptive immune response (immunoglobulins IgM, IgG, and IgA). Findings support further investigation of immunomodulatory approaches to treatment of glaucoma.

TRANSLATIONAL RELEVANCE

This study looks at the basic inflammatory pathways and biomarkers relevant to glaucoma.