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      Status of Systemic Oxidative Stresses in Patients with Primary Open-Angle Glaucoma and Pseudoexfoliation Syndrome

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          Abstract

          Background

          The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. To test this, we measured the systemic levels of prooxidants and antioxidants by analyzing the blood biochemistry in patients with glaucoma.

          Methods

          Peripheral blood samples were collected from Japanese patients with primary open-angle glaucoma (PG) (n = 206), exfoliation syndrome (EX) (n = 199), and controls (n = 126). Plasma levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured by diacron reactive oxygen metabolites (dROM), biological antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free radical analyzer.

          Results

          In the PG, EX, and control groups, the mean ± standard deviation values were 355±63, 357±69, and 348±56 (U. Carr), respectively, for dROM; 1,951±282, 1,969±252, and 2,033±252 (µmol/L), respectively, for BAP (µmol/L); and 614±98, 584±91, and 617±99 (µmol/L), respectively, for SH. The differences in the BAP values were significant between the PG and control groups (p = 0.0062), for SH between the EX and control groups (p = 0.0017), and for SH between the PG and EX groups (p = 0.0026). After adjustment for differences in age and sex among groups using multiple regression analysis, lower BAP values were correlated significantly with PG (p = 0.0155) and EX (p = 0.0049). Higher dROM values with and without glaucoma were correlated with female gender, and lower SH values with older age. There were no significant differences between the higher (≥21 mmHg) and lower (<21 mmHg) baseline IOPs in the PG group or between the presence or absence of glaucoma in the EX group.

          Conclusions

          Lower systemic antioxidant capacity that measured by ferric-reducing activity is involved in the pathogenesis of PG and EX.

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          Most cited references44

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          The role of oxidative stress in glaucoma.

          DNA damage is related to a variety of degenerative diseases such as cancer, atherosclerosis and neurodegenerative diseases, depending on the tissue affected. Increasing evidence indicates that reactive oxygen species (ROS) play a key role in the pathogenesis of primary open angle glaucoma (POAG), the main cause of irreversible blindness worldwide. Oxidative DNA damage is significantly increased in the ocular epithelium regulating aqueous humor outflow, i.e., the trabecular meshwork (TM), of glaucomatous patients compared to controls. The pathogenic role of ROS in glaucoma is supported by various experimental findings, including (a) resistance to aqueous humor outflow is increased by hydrogen peroxide by inducing TM degeneration; (b) TM possesses remarkable antioxidant activities, mainly related to superoxide dismutase-catalase and glutathione pathways that are altered in glaucoma patients; and (c) intraocular-pressure increase and severity of visual-field defects in glaucoma patients parallel the amount of oxidative DNA damage affecting TM. Vascular alterations, which are often associated with glaucoma, could contribute to the generation of oxidative damage. Oxidative stress, occurring not only in TM but also in retinal cells, appears to be involved in the neuronal cell death affecting the optic nerve in POAG. The highlighting of the pathogenic role of ROS in POAG has implications for the prevention of this disease as indicated by the growing number of studies using genetic analyses to identify susceptible individuals and of clinical trials testing the efficacy of antioxidant drugs for POAG management.
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            Prevalence and causes of low vision and blindness in a Japanese adult population: the Tajimi Study.

            To determine the prevalence and causes of low vision and blindness in a Japanese adult population. Population-based cross-sectional study. Randomly selected residents (n = 3870) of Tajimi City, Japan, who were 40 years of age or older. Of the 3021 study participants (78.1% of 3870 eligible persons), 2977 (76.9%) underwent a complete ophthalmologic examination including measurement of the best-corrected visual acuity (BCVA) with full subjective refraction using a Landolt ring chart at 5 m. Age- and gender-specific prevalence rates of low vision and blindness were estimated and causes were identified. Low vision and blindness were defined as BCVA in the better eye worse than 20/60 to a lower limit of 20/400 and worse than 20/400, respectively (World Health Organization [WHO] criteria) and worse than 20/40 but better than 20/200 and 20/200 or worse, respectively (United States criteria). The overall prevalence of blindness according to the WHO or U.S. criteria was 0.14% (n = 4; 95% confidence interval [CI], 0.06-0.32). The primary causes were optic atrophy, myopic macular degeneration, retinitis pigmentosa, and uveitis. The overall prevalence of low vision according to the WHO criteria was 0.39% (95% CI, 0.18%-0.60%) and according to the U.S. criteria was 0.98% (95% CI, 0.66%-1.30%), which was significantly greater in women and in the older half of the participants than in the younger half (P = 0.0079 and <0.0001, respectively). The leading causes of low vision in descending order were cataract followed by glaucoma, and those of monocular blindness were myopic macular degeneration, glaucoma, and trauma. The prevalence of low vision and blindness in Japanese adults was one of the lowest among those reported. The major causes of low vision were cataract and glaucoma, and the leading cause of monocular blindness was myopic macular degeneration.
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              The impact of Vision 2020 on global blindness.

              Recent data suggest that there are 37 million blind people and 124 million with low vision, excluding those with uncorrected refractive errors. The main causes of global blindness are cataract, glaucoma, corneal scarring (from a variety of causes), age-related macular degeneration, and diabetic retinopathy. It would appear that the global Vision 2020 initiative is having an impact to reduce avoidable blindness particularly from ocular infections, but more needs to be done to address cataract, glaucoma, and diabetic retinopathy.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                26 November 2012
                : 7
                : 11
                : e49680
                Affiliations
                [1]Department of Ophthalmology, Shimane University Faculty of Medicine, Izumo, Shimane, Japan
                Baker IDI Heart and Diabetes Institute, Australia
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MT SK YT AO. Performed the experiments: SK. Analyzed the data: MT. Contributed reagents/materials/analysis tools: MT YT. Wrote the paper: MT SK YT AO.

                Article
                PONE-D-12-18358
                10.1371/journal.pone.0049680
                3506654
                23189153
                f5204a44-2c6d-4325-b45f-1e71da31a500
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 June 2012
                : 12 October 2012
                Page count
                Pages: 7
                Funding
                This study was supported by research grants from the Imai Memorial Glaucoma Research Foundation, the Suda Memorial Glaucoma Research Foundation, and a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (JSPS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biochemistry
                Metabolism
                Oxygen Metabolism
                Blood Chemistry
                Molecular Cell Biology
                Cellular Stress Responses
                Chemistry
                Medicinal Chemistry
                Medicine
                Diagnostic Medicine
                Clinical Laboratory Sciences
                Clinical Chemistry
                Oncology
                Basic Cancer Research
                Oxidative Damage
                Ophthalmology
                Glaucoma

                Uncategorized
                Uncategorized

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