Autoinflammation and Autoimmunity in the Aqueous Humor of Glaucoma Patients

Abstract

Purpose : Recent studies into the pathophysiology of glaucomatous optic neuropathy have highlighted the importance of autoinflammation and autoimmunity in the disease process. We explored the hypothesis that various neutrophil related markers are elevated in the aqueous humor of glaucoma patients compared to controls.

Methods : We recruited patients scheduled to undergo cataract extraction and/or glaucoma surgery. Study approval was obtained from the Institutional Review Board of the University of Illinois at Chicago (UIC). Informed consent was obtained from all participants after the nature and possible consequences of the study were explained. A total of 177 eyes were included in the study, of which 127 were controls, 43 glaucoma patients, and 7 uveitis patients.

Results : We found that many inflammatory markers are elevated in the aqueous humor of glaucoma patients as compared to controls. Pro-inflammatory markers such as IL-1a (p=0.0028) and IL-1b (p<0.0001); T-cell chemoattractant interferon gamma-inducible protein 10 (IP-10) (p=0.0002); neutrophil markers IL-8 (p<0.0001) and neutrophil gelatinase-associated lipocalin (NGAL) (p<0.0001); and the neutrophil extracellular trap (NET) marker eDNA (p<0.0001) are increased. Furthermore, IgG subtypes (IgG1 [p<0.0001], IgG2 [p=0.0039], IgG3 [p<0.0001], IgG4 [p=0.0237]) as well as IgA (p=0.0011) and IgM (p=0.0330) are found in higher concentrations within aqueous humor of glaucoma patients than controls.
We also found that levels of eDNA significantly correlate with IgG, especially in patients with glaucoma (r²=0.62, p<0.0001).

Conclusions : The data presented provides exciting new advances in the understanding of glaucoma. Using a large sample size of aqueous humor, we are able to demonstrate increased concentrations of various inflammatory markers in glaucomatous eyes. Multiple levels of the inflammatory pathway are implicated, including inflammatory cytokines (IL-1a and IL-1b), T-cell mediators (IP-10), neutrophil chemoattractant (IL-8), NET-associated molecules (NGAL and eDNA), and the adaptive immune response (immunoglobulins IgG and IgA).

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.