29
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Oxidative DNA damage and total antioxidant status in glaucoma patients

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose

          To evaluate DNA damage markers and the antioxidant status of serum and aqueous humor in glaucoma patients.

          Methods

          Aqueous humor and serum samples were obtained at the time of surgery from 28 patients with glaucoma and 27 patients with cataracts. Total antioxidant status (TAS) and 8-hydroxy-2´-deoxyguanosine (8-OHdG) levels of all samples were determined by spectrophotometric and enzyme-linked immunosorbent assay methods.

          Results

          Aqueous levels of 8-OHdG were higher in glaucoma patients than in the cataract group (4.61±2.97 ng/ml versus 1.98±0.70 ng/ml, p=0.002). Serum levels of 8-OHdG were also higher in glaucoma patients than in the cataract group (17.80±8.06 ng/ml versus 13.63±3.54 ng/ml, p=0.046). The TAS levels of serum (0.55±0.13 mmol/lit versus 0.70±0.14, p=0.001), and aqueous humor (0.23±0.13 mmol/lit versus 0.34±0.15, p=0.001) in glaucoma patients were lower than in cataract patients.

          Conclusions

          Our findings provide evidence that oxidative DNA damage increases and TAS decreases in the serum and aqueous humor of glaucoma patients. These findings support the hypothesis that the formation of reactive oxygen species and/or a decrease in TAS may have an important role in the pathogenesis of glaucoma.

          Related collections

          Most cited references33

          • Record: found
          • Abstract: found
          • Article: not found

          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.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients.

            Little is known about the molecular mechanisms responsible for the development of glaucoma, the leading cause of irreversible blindness worldwide. Some investigators have hypothesized that oxidative damage may be involved. We evaluated oxidative deoxyribonucleic acid (DNA) damage, in terms of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the eyes of glaucoma patients. Levels of 8-OH-dG were measured in the trabecular meshwork region from 42 patients with glaucoma and 45 controls of similar age and sex. Genotypes of glutathione S-transferase isoenzymes (GSTM1 and GSTT1) were assessed by polymerase chain reaction in the same DNA samples. Levels of 8-OH-dG were significantly higher in glaucoma patients than in controls. Oxidative DNA damage in patients with glaucoma correlated significantly with intraocular pressure; in patients with primary open-angle glaucoma, it also correlated with visual field defects. GSTT1 was similar in the two groups, and had no effect on 8-OH-dG levels. Conversely, 8-OH-dG levels were significantly higher in GSTM1-null than in GSTM1-positive subjects. The GSTM1-null genotype was significantly more common in patients with primary open-angle glaucoma than in controls. Oxidative DNA damage is significantly increased in the trabecular meshwork of glaucoma patients. GSTM1 gene deletion, which has been associated with an increased risk of cancer at various sites and molecular lesions in atherosclerosis, predisposes to more severe oxidative DNA damage in glaucoma patients. These findings may contribute to understanding the pathogenesis of glaucoma and may be useful in the prevention and treatment of this disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Glaucomatous outflow pathway and oxidative stress.

              Oxidative free radicals and reactive oxygen species (ROS) are able to affect the cellularity of the human trabecular meshwork (HTM). These findings suggest that intraocular pressure increase, which characterises most glaucomas, is related to oxidative degenerative processes affecting the HTM and specifically its endothelial cells. Much evidence indicates that in this region ROS play a fundamental pathogenic role by reducing local antioxidant activities, inducing outflow resistance and exacerbating the activities of superoxide dismutase and glutathione peroxidase in glaucomatous eyes. Furthermore, hydrogen peroxide induces rearrangement of HTM cells and compromises their integrity. Glaucomatous subjects might have a genetic predisposition rendering them more susceptible to ROS-induced damage. A fairly significant correlation between oxidative DNA damage in the HTM and intraocular pressure increase and visual field defects in glaucomatous patients has been demonstrated. Thus, oxidative stress may play a significant role during glaucoma course initially damaging HTM cells, then contributing to the alteration of the homeostasis between NO and endothelins, and finally through its possible involvement in ganglional cell death. On the whole, these findings support the hypothesis that oxidative damage is an important step in the pathogenesis of primary open-angle glaucoma, and might be a relevant target for both prevention and therapy.
                Bookmark

                Author and article information

                Journal
                Mol Vis
                MV
                Molecular Vision
                Molecular Vision
                1090-0535
                2011
                07 January 2011
                : 17
                : 41-46
                Affiliations
                [1 ]Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                [2 ]Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                Author notes
                Correspondence to: A Ghorbanihaghjo, 2Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz 51664, Iran; Phone: 0098-411-6551332; FAX: 0098-411-6577336; email: ghorbaniamir@ 123456hotmail.com
                Article
                6 2010MOLVIS0046
                3021573
                21245957
                e99e99ce-9943-43a6-947d-45bf0fad5071
                Copyright © 2011 Molecular Vision.

                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 work is properly cited.

                History
                : 14 February 2010
                : 04 January 2011
                Categories
                Research Article
                Custom metadata
                Export to XML
                Ghorbanihaghjo

                Vision sciences
                Vision sciences

                Comments

                Comment on this article