Abstract

We previously reported that lower systemic antioxidant capacity is involved in primary open-angle glaucoma (POAG) and exfoliation syndrome pathogeneses as measured by ferric-reducing activity. In the present study, we measured hydroxylinoleate (HODE) and hydroxyarachidonate (HETE) isomer serum levels after sample reduction and saponification to investigate POAG pathogenesis. POAG patients (n = 198) were recruited and divided into normal- and high-tension glaucoma groups (n = 84 and 114, respectively) depending on intraocular pressure. 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. Enzymatic and singlet oxygen-mediated fatty acid oxidation may be major pathways of oxidation process in glaucoma subjects.

Highlights

  • Isomer serum levels after sample reduction and saponification to investigate primary open-angle glaucoma (POAG) pathogenesis

  • Evidence suggests that oxidative stress is involved in intraocular pressure (IOP) elevation and retinal ganglion cells (RGCs) loss in POAG and in POAG without marked IOP elevation such as in normal-tension glaucoma (NTG)

  • We previously reported lower systemic antioxidant capacity measured by ferric-reducing activity in patients with POAG and glaucoma secondary to exfoliation syndrome compared with controls[17]

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Summary

Introduction

Isomer serum levels after sample reduction and saponification to investigate POAG pathogenesis. 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. We proposed totally assessed hydroxylinoleates (HODEs) from biological samples as biomarkers for investigations of pathogenesis, disease progression, and prognosis[1,2,3,4]. The absolute concentrations of lipid hydroperoxides in vivo are considered minimal since they are substrates of many enzymes such as glutathione peroxidases and phospholipases In such cases, the stable oxidation products are HODEs. Our method for measuring totally assessed HODE is characterized by the reduction and saponification of samples beforehand. We investigated the involvement of oxidative stress in this disease by using our own proposed oxidative stress marker HODEs and HETEs quantitatively

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