Anti-Inflammatory Cytokine Signatures in Primary Glaucoma Subtypes: Diagnostic and Pathophysiological Insights From IL-36Ra, IL-37, and IL-38.

Abstract

Objectives: To quantify interleukin-36 receptor antagonist (IL-36Ra), interleukin-37 (IL-37), and interleukin-38 (IL-38) levels in aqueous humor and plasma of patients with primary glaucoma, and investigate their correlations with glaucomatous structural damage.

Methods: Matched aqueous humor and plasma samples were collected from patients with acute primary angle-closure glaucoma (APACG), chronic PACG (CPACG), and primary open-angle glaucoma (POAG), and age-related cataract controls (ARC). Levels of IL-36Ra, IL-37, and IL-38 were quantified and correlated with average retinal nerve fiber layer thickness (RNFLT).

Results: A total of 96 participants were enrolled, including 25 APACG, 23 CPACG, 23 POAG, and 25 ARC. In aqueous humor, IL-36Ra was significantly elevated in CPACG compared to all other groups, while IL-37 and IL-38 were markedly increased in both CPACG and POAG compared to ARC and APACG (all p < 0.05). In plasma, IL-36Ra was significantly lower in the POAG and APACG than in ARC and CPACG, and IL-38 was reduced in APACG compared to all other groups (all p < 0.05). All three cytokines in aqueous humor, as well as plasma IL-36Ra and IL-38, showed significant negative correlations with average RNFLT. Notably, aqueous humor IL-38 exhibited the strongest association with RNFLT, particularly within the POAG (r = -0.745, p < 0.001) and CPACG (r = -0.496, p = 0.016) subgroups, suggesting an association with structural damage in chronic glaucoma.

Conclusion: Aqueous humor IL-38 levels correlated with RNFLT thinning in POAG and CPACG, suggesting a potential role as a biomarker associated with structural damage. IL-36Ra was independently elevated in CPACG, supporting its potential as a subtype-related biomarker. Further studies are needed to clarify the mechanisms of these cytokines in glaucoma pathogenesis.