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      Superoxide Dismutase1 Levels in North Indian Population with Age-Related Macular Degeneration

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          Abstract

          Aim. The aim of the study was to estimate the levels of superoxide dismutase1 (SOD1) in patients of age-related macular degeneration (AMD) and examine the role of oxidative stress, smoking, hypertension, and other factors involved in the pathogenesis of AMD. Methods. 115 AMD patients and 61 healthy controls were recruited for this study. Serum SOD1 levels were determined by ELISA and were correlated to various risk factors. Logistic regression model of authenticity, by considering SOD1 as independent variable, has been developed along with ROC curve. Results. The SOD1 levels were significantly higher in AMD patients as compared to those of the controls. The difference was not significant for wet and dry AMD. However, the difference was significant between wet AMD subtypes. Nonsignificance of the Hosmer-Lemeshow goodness of fit statistic ( χ 2 = 10.516, df = 8, P = 0.231) indicates the appropriateness of logistic regression model to predict AMD. Conclusion. Oxidative stress in AMD patients may mount compensatory response resulting in increased levels of SOD1 in AMD patients. To predict the risk of AMD on the basis of SOD1, a logistic regression model shows authenticity of 78%, and area under the ROC curve (0.827, P = .0001) with less standard error of 0.033 coupled with 95% confidence interval of 0.762–0.891 further validates the model.

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          Most cited references47

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          The role of oxidative stress in the pathogenesis of age-related macular degeneration.

          Age-related macular degeneration (AMD) is the leading cause of blind registration in the developed world, and yet its pathogenesis remains poorly understood. Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates (ROI), has been implicated in many disease processes, especially age-related disorders. ROIs include free radicals, hydrogen peroxide, and singlet oxygen, and they are often the byproducts of oxygen metabolism. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to visible light. In vitro studies have consistently shown that photochemical retinal injury is attributable to oxidative stress and that the antioxidant vitamins A, C, and E protect against this type of injury. Furthermore, there is strong evidence suggesting that lipofuscin is derived, at least in part, from oxidatively damaged photoreceptor outer segments and that it is itself a photoreactive substance. However, the relationships between dietary and serum levels of the antioxidant vitamins and age-related macular disease are less clear, although a protective effect of high plasma concentrations of alpha-tocopherol has been convincingly demonstrated. Macular pigment is also believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching ROIs. Many putative risk-factors for AMD have been linked to a lack of macular pigment, including female gender, lens density, tobacco use, light iris color, and reduced visual sensitivity. Moreover, the Eye Disease Case-Control Study found that high plasma levels of lutein and zeaxanthin were associated with reduced risk of neovascular AMD. The concept that AMD can be attributed to cumulative oxidative stress is enticing, but remains unproven. With a view to reducing oxidative damage, the effect of nutritional antioxidant supplements on the onset and natural course of age-related macular disease is currently being evaluated.
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            Incidence of legal blindness from age-related macular degeneration in denmark: year 2000 to 2010.

            To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older. Population-based observational registry study. settings: Membership register of the Danish Association of the Blind, the primary admission criterion of which is best-corrected visual acuity 0.1 (20/200) or lower in a person's better-seeing eye. study population: A total of 11 848 incident cases of legal blindness from a population of citizens aged ≥50 years numbering 1.71 million in 2000 and 1.87 million in 2010 with free access to a single-payer public health care system. main outcome measures: Incidence rates of legal blindness from AMD from 2000 to 2010. The incidence rate of legal blindness attributable to AMD in citizens aged ≥50 years decreased from 52.2 cases per year per 100 000 in 2000 to 25.7 cases per year per 100 000 in 2010, corresponding to a reduction of 50% (95% confidence interval [CI(95)]: 45%-56%, P < .0001, adjusted for age), the bulk of the reduction occurring after 2006. The incidence of legal blindness from causes other than AMD decreased by 33% (CI(95): 21%-44%, P < .0001), most of the reduction occurring between 2000 and 2006. From 2000 to 2010 the incidence of legal blindness from AMD fell to half the baseline incidence. The bulk of the reduction occurred after the introduction of intravitreally injected inhibitors of vascular endothelial growth factor in 2006. Copyright © 2012 Elsevier Inc. All rights reserved.
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              SOD2 knockdown mouse model of early AMD.

              To test the hypothesis that oxidative injury to the retinal pigment epithelium (RPE) may lead to retinal damage similar to that associated with the early stages of age-related macular degeneration (AMD). A ribozyme that targets the protective enzyme manganese superoxide dismutase (MnSOD) was expressed in RPE-J cells, and adeno-associated virus (AAV) expressing the ribozyme gene was injected beneath the retinas of adult C57BL/6 mice. The RPE/choroid complex was examined for SOD2 protein levels and protein markers of oxidative damage using immunoblot analysis and LC MS/MS-identification of proteins and nitration sites. Lipids were extracted from retinal tissue and analyzed for the bis-retinoid compounds A2E and iso-A2E. The mice were analyzed by full-field electroretinography (ERG) for light response. Light and electron microscopy were used to measure cytological changes in the retinas. The treatment of RPE-J cells with Rz432 resulted in decreased MnSOD mRNA and protein as well as increased levels of superoxide anion and apoptotic cell death. When delivered by AAV, Rz432 reduced MnSOD protein and increased markers of oxidative damage, including nitrated and carboxyethylpyrrole-modified proteins in the RPE-choroid of mice. Ribozyme delivery caused a progressive loss of electroretinograph response, vacuolization, degeneration of the RPE, thickening of Bruch's membrane, and shortening and disorganization of the photoreceptor outer and inner segments. Progressive thinning of the photoreceptor outer nuclear layer resulted from apoptotic cell death. Similar to the eyes of patients with AMD, ribozyme-treated eyes exhibited increased autofluorescence and elevated levels of A2E and iso-A2E, major bis-retinoid pigments of lipofuscin. These results support the hypothesis that oxidative damage to the RPE may play a role in some of the key features of AMD.
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                Author and article information

                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OXIMED
                Oxidative Medicine and Cellular Longevity
                Hindawi Publishing Corporation
                1942-0900
                1942-0994
                2013
                30 November 2013
                : 2013
                : 365046
                Affiliations
                1Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
                2Department of Ophthalmology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
                3Department of Statistics, Panjab University, Chandigarh 160014, India
                Author notes

                Academic Editor: Peter Shaw

                Author information
                http://orcid.org/0000-0001-9003-3532
                Article
                10.1155/2013/365046
                3864086
                24363822
                1c1afac0-b87f-4a1d-8811-bf67d498cf1b
                Copyright © 2013 Akshay Anand et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 April 2013
                : 20 October 2013
                : 28 October 2013
                Funding
                Funded by: http://dx.doi.org/10.13039/501100001411 Indian Council of Medical Research
                Award ID: 45/11/2010-HUM/BMS
                Categories
                Clinical Study

                Molecular medicine
                Molecular medicine

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