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.