Increased Levels of Interleukin-6 in the Aqueous Humor of Patients with Early Stages of Pseudoexfoliation Syndrome/ Glaucoma

Abstract

Purpose:: Subtle inflammatory conditions have been implicated in initial stages of various systemic fibrotic disorders. To determine the role of inflammatory processes in the pathophysiology of pseudoexfoliation (PEX) syndrome/ glaucoma, we examined the presence and expression of (pro-) inflammatory cytokines in eyes from PEX and control patients.

Methods:: Patients were classified as early or late stages of PEX syndrome according to graded slitlamp findings of PEX material deposits on lens and pupillary margin. Aqueous humor samples from patients with cataract, primary open-angle glaucoma (POAG), early and late stages of PEX syndrome with and without glaucoma (n=14 for each patient group) were analyzed for twenty different cytokines by multiplex-bead immunoassay. In addition, aqueous IL-6 concentrations were measured by ELISA (n=12 for each group), and mRNA expression of IL-6 in the ciliary body was quantified by real-time PCR (n=4 for each group).

Results:: Multiplex-bead immunoassay revealed a statistically signifcant increase of aqueous IL-6 levels in patients with early stages of PEX syndrome (p<0.002). Differences in aqueous IL-6 levels were confirmed by ELISA displaying a specific increase in early stages of PEX syndrome with (1.9-fold; p<0.001) and without glaucoma (2.3-fold; p<0.002) as compared to cataract, POAG, and late stages of PEX syndrome with and without glaucoma. Quantitative real-time PCR showed a statistically significant increase of IL-6 mRNA expression in the ciliary processes of early stages of PEX syndrome/ glaucoma (2-fold; p<0.003) compared with all other groups of patients.

Conclusions:: In view of the involvement of inflammatory cytokines in early stages of fibrotic disorders, such as lung fibrosis, these findings suggest that low-grade subclinical inflammatory processes, reflected by increased levels of IL-6, may play a pathophysiological role in initial stages of the abnormal matrix metabolism characteristic of PEX syndrome.

Keywords: cytokines/chemokines • extracellular matrix • gene/expression