Abstract
Purpose :
We previously reported that lower systemic antioxidant capacity measured by ferric-reducing activityis associated with intraocular pressure elevation in primary open-angle glaucoma (POAG) and exfoliation syndrome.In the present study, to investigate glaucoma pathogenesis, we comprehensively measured serum levels of hydroxylinoleate (HODE) and hydroxyarachidonate (HETE) isomers, oxidation products of linoleates and arachidonates, respectively, in POAG and control (CT) subjects.
Methods :
A total of 317 Japanese subjects comprised the POAG (n = 198) and non-glaucomatous CT (n = 119) groups. Various HODEs, HETEs, and their parent molecules—i.e., linoleic acids and arachidonic acids—were detected using the same protocol. After sample reduction and saponification,an aliquot of the sample was analyzed by liquid chromatography/tandem mass spectrometry (LC-MS/MS) on a TSQ Quantum Access Max system (Thermo Fisher Scientific, Waltham, MA, USA).
Results :
Total HODE (/linoleic acid) and HETE (/arachidonic acid) serum levels were significantly higher in the POAG group (211.9 ± 143.0 and 181.0 ± 164.1 µmol/mol, respectively) than in controls (167.1 ± 105.2 and 132.5 ± 139.7 µmol/mol, p = 0.0025 and 0.0101, respectively). The associations between HODEs/HETEs and glaucoma were further confirmed by multivariate analyses after adjusting for differences in demographic parameters. Among the HODE isomers, the levels of 9- and 13-(Z,E)-HODEs (p = 0.0014) and singlet oxygen-specific products (i.e., 10- and 12-(Z,E)-HODEs, p = 0.0345) were higher in the POAG group than in controls, while free radical-mediated oxidation-specific products (i.e., 9- and 13-(E,E)-HODEs, p = 0.0557) demonstrated a marginal difference.
Conclusions :
Systemic oxidation was involved in the pathogenesis of glaucoma. The major pathways may be enzymatic and singlet oxygen-mediated lipid peroxidation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.