Evaluation of Redox Profiles of the Serum and Aqueous Humor in Patients with Primary Open-Angle Glaucoma and Exfoliation Glaucoma

Abstract

Oxidative stress is thought to play a significant role in the development of glaucoma. However, the association between systemic and local oxidative stresses in different types of glaucoma has not been assessed fully. The current study compared the redox status in the aqueous humor (AH) and blood samples among eyes with primary open-angle glaucoma (POAG), exfoliation glaucoma (EXG), and non-glaucomatous controls to evaluate the relationship among systemic redox status, intraocular oxidative stress, and clinical backgrounds. AH and blood samples were obtained from 45 eyes of 45 Japanese subjects (15 POAG, 15 EXG, and 15 control eyes). The serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer. The activities of cytosolic and mitochondrial forms of the superoxide dismutase (SOD) isoforms, i.e., SOD1 and SOD2, respectively, in AH and serum were measured using a multiplex bead immunoassay. In AH, SOD1 in subjects with EXG and SOD2 in those with POAG and EXG were significantly higher than in control eyes. In serum, compared to control subjects, BAP in subjects with POAG and EXG was significantly lower; SOD1 in those with EXG and SOD2 in those with POAG and EXG were significantly higher. dROM and SH did not differ significantly among the groups. The BAP values were correlated negatively with the SOD1 concentrations in AH and serum, SOD2 in the AH, intraocular pressure, and number of antiglaucoma medications. In conclusion, lower systemic antioxidant capacity accompanies up-regulation of higher local antioxidant enzymes, suggesting increased oxidative stress in eyes with OAG, especially in EXG. Determination of the systemic BAP values may help predict the redox status in AH.

Metabolomics in Primary Open Angle Glaucoma: A Systematic Review and Meta-Analysis

“…Among these studies, some changes were found to be common in several reports and share similar or overlapping metabolic pathways. For instance, significant upregulation of the metabolites in responding to oxidative stress was reported in both studies by Buisset et al (2019) and Takayanagi et al (2020) , in agreement with increased oxidative stress in patients with POAG. Mitochondrial energetic substrates were also noted in several of the studies, indicating dysregulated energy metabolism in patients with POAG ( Leruez et al, 2018 ; Kouassi Nzoughet et al, 2020 ).…”

Metabolomics in Retinal Diseases: An Update

“…With respect to pathophysiological mechanisms, oxidative stress plays an important role in the development of glaucoma. Takayanagi et al [121] explored the association between systemic and local oxidative stresses in POAG and PEXG by utilizing a metabolomics approach. They drew a conclusion that a low level of systemic antioxidant capacity was observed, along with up-regulation of antioxidant enzymes in aqueous humor, suggesting elevated oxidative stress in eyes with POAG, particularly in PEXG.…”

Fingertip-Measured Skin Carotenoids and Advanced Glycation End Product Levels in Glaucoma

“…ROS is mainly generated by the metabolism of the mitochondria and neutralized by antioxidants [ 15 ]. We previously reported that lower levels of serum biologic antioxidant potential were correlated with higher levels of IOP and with greater visual field loss in primary open-angle glaucoma (PG) [ 16 , 17 , 18 ].…”

“…As part of our ongoing research program directed toward the analysis of the relationship between ophthalmologic disorders and stress markers measured by fingertip measurements [ 16 , 17 , 18 ], we investigated the clinical factors including SC and AGEs levels with glaucoma types. We previously reported AGEs levels in PG and EG [ 40 ]; however, the relationship between SC levels and glaucoma has not been reported.…”