Positive Association between Aqueous Humor Hydroxylinoleate Levels and Intraocular Pressure

We previously proposed the total assessment of hydroxylinoleates (HODEs) by LC-MS/MS after saponification and reduction of the biologic samples as biomarkers to investigate pathogenesis, disease progression, and prognosis. In this study, HODE levels were estimated in aqueous humor (AH) samples from 63 eyes (41 Japanese subjects; 15 men; mean age, 77.3 ± 6.8 years) with primary open-angle glaucoma (POAG) or cataracts. The correlations between intraocular HODE levels and background parameters, including intraocular pressure (IOP), were analyzed to assess the possible involvement of oxidative stress in glaucoma pathology. Univariate analyses showed that linoleic acid (LA) (p = 0.034) and arachidonic acid (AA) (p = 0.0041) levels were associated negatively with age; 13-(Z,E)-HODE (p = 0.018) and 13-(E,E)-HODE (p = 0.021) were associated positively with IOP; 9-(Z,E)-HODE (p = 0.039), 13-(Z,E)-HODE (p = 0.021), totally assessed-HODE (t-HODE, p = 0.023), LA (p = 0.0080), and AA (p = 0.0051) were higher in eyes with glaucoma than cataract. No gender differences were seen. A mixed-effect regression model showed that higher 13-(Z,E)-HODE (p = 0.0040) and higher t-HODE (p = 0.040) were associated with glaucoma rather than cataracts; and higher levels of 13-(Z,E)-HODE/LA (p = 0.043), 13-(E,E)-HODE/LA (p = 0.042), 13-(Z,E)-HODE (p = 0.0054), and 13-(E,E)-HODE (p = 0.027) were associated with higher IOP. Linoleate-derived oxidation products were quantified successfully in AH samples from patients with glaucoma and cataracts. A free radical oxidation mechanism can be associated with IOP elevation, while enzymatic oxidation may be involved, specifically, in the pathogenesis of POAG.