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. 2026 Jan 5;15(1):29.
doi: 10.1167/tvst.15.1.29.

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

Eitan A Katz  1 , Yang Yang  1 , Bayasgalan Surenkhuu  1 , Zeenal Dabre  1 , Azza Dammak  2   3 , Vidhya R Rao  3 , Christine Mun  1 , Anubhav Pradeep  1 , Christian Kim  1 , Ahmad A Aref  1 , Pooja Bhat  1 , Jose de la Cruz  1 , Simon Kaja  3   4 , Sandeep Jain  1
Affiliations

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

Eitan A Katz et al. Transl Vis Sci Technol. .

Abstract

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.

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Conflict of interest statement

Disclosure: E.A. Katz, None; Y. Yang, None; B. Surenkhuu, None; Z. Dabre, None; A. Dammak, None; V.R. Rao, None; C. Mun, None; A. Pradeep, None; C. Kim, None; A.A. Aref, Abbvie (F), Alcon (R), Nova Eye Medical (F), New World Medical (C); P. Bhat, None; J. de la Cruz, None; S. Kaja, None; S. Jain, Neutrolis Inc. (C, P), Amgen (C, P), Selagine Inc. (I), Advaite Inc. (I)

Figures

Figure 1.
Figure 1.
Concentration of significantly different inflammatory markers in AH of patients with cataract and glaucoma. (A) Elevated levels of neutrophil-related markers eDNA, IL-8, and NGAL in glaucoma AH as compared with cataracts. (B) Additional cytokine levels in the AH of patients with glaucoma compared with controls with elevation of IP-10, IL-1β, TNF-α, and decreased levels of LIGHT in glaucomatous eyes.
Figure 2.
Figure 2.
Concentration of immunoglobulins in AH of patients with cataract and glaucoma. Immunoglobulin concentrations in the AH of patients with glaucoma compared with controls with elevation of total immunoglobulins, IgG, IgM, IgA, and subtypes IgG1 to IgG4.
Figure 3.
Figure 3.
Correlation of eDNA in the AH to other inflammatory markers. The eDNA has significant correlation to IgG, IL-8, NGAL, and IP-10 in both glaucomatous eyes and controls with stronger correlation in patients with glaucoma.
Figure 4.
Figure 4.
Correlation of eDNA in the AH to glaucoma testing parameters. (A) The eDNA has a significant negative correlation with inferior RNFL thickness as measured with OCT. (B) The eDNA has a positive correlation with PSD as measured by HVF. Control patients did not have routine HVF or OCT performed for analysis. HVF, Humphrey visual field; OCT, optical coherence tomography; PSD, pattern standard deviation; RNFL, retinal nerve fiber layer.
Figure 5.
Figure 5.
Concentration of inflammatory markers in AH by severity of glaucoma. (A) The eDNA in the AH is significantly elevated in severe stage glaucoma when compared to the mild/moderate stage. (B) NGAL in the AH is significantly elevated in severe stage glaucoma compared to the mild/moderate stage. (C) IL-8 is trending toward statistically significant elevation in severe stage glaucoma compared to mild/moderate stage. (D) IP-10 is trending toward statistically significant elevation in severe stage glaucoma compared to the mild/moderate stage.
Figure 6.
Figure 6.
Random Forest Model. (A) ROC curve demonstrates good predictive capability with reproducible results on testing. (B) Graphical representation of feature importance score with markers listed from most important to least important in regard to the model.
See this image and copyright information in PMC

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