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

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.