Involvement of free radical-mediated oxidation in the pathogenesis of pseudoexfoliation syndrome detected based on specific hydroxylinoleate isomers.

We reported previously that enzymatic and singlet oxygen-mediated fatty acid oxidation may be major oxidation pathways in subjects with primary open angle glaucoma, based on measurement of serum levels of hydroxylinoleate (HODE) and hydroxyarachidonate (HETE) isomers after reduction and saponification. In this study, we measured serum levels of HODE and HETE isomers to investigate the pathogenesis of exfoliation syndrome (EX). In total, 311 Japanese subjects comprising EX patients (n = 192) and non-glaucomatous control subjects (n = 119) were included in this study. Patients with EX (n = 192) were divided into EX with glaucoma (EXG) and EX without glaucoma (EXS) groups (n = 128 and n = 64, respectively) depending on the intraocular pressure. Total HODE (/linoleic acid) serum levels were significantly (p = 0.0426) higher in the EX group (202.7 ± 153.2 μmol/mol) than in the controls (167.1 ± 105.3 μmol/mol). Among the HODE isomers, the levels of 9-(E,E)-HODEs (p < 0.0001) and 13-(E,E)-HODEs (p < 0.0001), both free radical-mediated oxidation products, were higher in the EX and EXG groups than in the controls, whereas no significant difference was observed between EXS and controls. After adjusting for differences in demographic parameters, multivariate analyses confirmed the association between 9- and 13-(E,E)-HODEs and EX. This is the first report of a dramatic increase in free radical-mediated oxidation products related to the pathogenesis of EX, and our findings suggest that free radical-mediated oxidation can be one of the causes of deterioration in EX.