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      Strategies to Reduce Oxidative Stress in Glaucoma Patients

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          Abstract

          Background:

          Primary open-angle glaucoma (POAG) is a multifactorial pathology

          involving a variety of pathogenic mechanisms, including oxidative/nitrosative stress. This latter is the consequence of the imbalance between excessive formation and insufficient protection against reactive oxygen/nitrogen species.

          Objective:

          Our main goal is to gather molecular information to better managing pathologic variants that may determine the individual susceptibility to oxidative/nitrosative stress (OS/NS) and POAG.

          Method:

          An extensive search of the scientific literature was conducted using PUBMED, the Web of Science, the Cochrane Library, and other references on the topic of POAG and OS/NS from human and animal model studies published between 2010 and 2017. Finally, 152 works containing relevant information that may help understanding the role of antioxidants, essential fatty acids, natural compounds and other similar strategies for counteracting OS/NS in POAG were considered.

          Results:

          A wide variety of studies have proven that antioxidants, among them vitamins B3, C and E, Coenzyme Q10 or melatonin, ω-3/ω-6 fatty acids and other natural compounds (such as coffee, green tea, bear bile, gingko biloba, coleus, tropical fruits, etc.,) may help regulating the intraocular pressure as well as protecting the retinal neurons against OS/NS in POAG.

          Conclusion:

          Based on the impact of antioxidants and ω-3/ω-6 fatty acids at the molecular level in the glaucomatous anterior and posterior eye segments, further studies are needed by integrating all issues involved in glaucoma pathogenesis, endogenous and exogenous risk factors and their interactions that will allow us to reach newer effective biotherapies for preventing glaucomatous irreversible blindness.

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          Most cited references117

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          The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults

          The reactive oxygen species (ROS) form under normal physiological conditions and may have both beneficial and harmful role. We search the literature and current knowledge in the aspect of ROS participation in the pathogenesis of anterior and posterior eye segment diseases in adults. ROS take part in the pathogenesis of keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, stimulating apoptosis of corneal cells. ROS play a role in the pathogenesis of glaucoma stimulating apoptotic and inflammatory pathways on the level of the trabecular meshwork and promoting retinal ganglion cells apoptosis and glial dysfunction in the posterior eye segment. ROS play a role in the pathogenesis of Leber's hereditary optic neuropathy and traumatic optic neuropathy. ROS induce apoptosis of human lens epithelial cells. ROS promote apoptosis of vascular and neuronal cells and stimulate inflammation and pathological angiogenesis in the course of diabetic retinopathy. ROS are associated with the pathophysiological parainflammation and autophagy process in the course of the age-related macular degeneration.
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            The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration.The AGIS Investigators.

            (2000)
            To investigate the association between control of intraocular pressure after surgical intervention for glaucoma and visual field deterioration. In the Advanced Glaucoma Intervention Study, eyes were randomly assigned to one of two sequences of glaucoma surgery, one beginning with argon laser trabeculoplasty and the other trabeculectomy. In the present article we examine the relationship between intraocular pressure and progression of visual field damage over 6 or more years of follow-up. In the first analysis, designated Predictive Analysis, we categorize 738 eyes into three groups based on intraocular pressure determinations over the first three 6-month follow-up visits. In the second analysis, designated Associative Analysis, we categorize 586 eyes into four groups based on the percent of 6-month visits over the first 6 follow-up years in which eyes presented with intraocular pressure less than 18 mm Hg. The outcome measure in both analyses is change from baseline in follow-up visual field defect score (range, 0 to 20 units). In the Predictive Analysis, eyes with early average intraocular pressure greater than 17.5 mm Hg had an estimated worsening during subsequent follow-up that was 1 unit of visual field defect score greater than eyes with average intraocular pressure less than 14 mm Hg (P =.002). This amount of worsening was greater at 7 years (1.89 units; P <.001) than at 2 years (0.64 units; P =.071). In the Associative Analysis, eyes with 100% of visits with intraocular pressure less than 18 mm Hg over 6 years had mean changes from baseline in visual field defect score close to zero during follow-up, whereas eyes with less than 50% of visits with intraocular pressure less than 18 mm Hg had an estimated worsening over follow-up of 0.63 units of visual field defect score (P =.083). This amount of worsening was greater at 7 years (1.93 units; P <.001) than at 2 years (0.25 units; P =.572). In both analyses low intraocular pressure is associated with reduced progression of visual field defect, supporting evidence from earlier studies of a protective role for low intraocular pressure in visual field deterioration.
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              Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group.

              (1998)
              To determine if intraocular pressure plays a part in the pathogenic process of normal-tension glaucoma. One eye of each eligible subject was randomized either to be untreated as a control or to have intraocular pressure lowered by 30% from baseline. Eyes were randomized if they met criteria for diagnosis of normal-tension glaucoma and showed documented progression or high-risk field defects that threatened fixation or the appearance of a new disk hemorrhage. The clinical course (visual field and optic disk) of the group with lowered intraocular pressure was compared with the clinical course when intraocular pressure remained at its spontaneous untreated level. One hundred-forty eyes of 140 patients were used in this study. Sixty-one were in the treatment group, and 79 were untreated controls. Twenty-eight (35%) of the control eyes and 7 (12%) of the treated eyes reached end points (specifically defined criteria of glaucomatous optic disk progression or visual field loss). An overall survival analysis showed a statistically significant difference between the two groups (P < .0001). The mean survival time +/-SD of the treated group was 2,688 +/- 123 days and for the control group, 1,695 +/- 143 days. Of 34 cataracts developed during the study, 11 (14%) occurred in the control group and 23 (38%) in the treated group (P = .0075), with the highest incidence in those whose treatment included filtration surgery. Intraocular pressure is part of the pathogenic process in normal-tension glaucoma. Therapy that is effective in lowering intraocular pressure and free of adverse effects would be expected to be beneficial in patients who are at risk of disease progression.
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                Author and article information

                Journal
                Curr Neuropharmacol
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers
                1570-159X
                1875-6190
                August 2018
                August 2018
                : 16
                : 7
                : 903-918
                Affiliations
                Ophthalmic Research Unit Santiago Grisolía/FISABIO, and Cellular and Molecular Research Unit, University of Valencia , Valencia, , Spain; Spanish Net of Ophthalmic Pathology OFTARED, Institute of Health Carlos III , Madrid, , Spain; Department of Preventive Medicine & Public Healh, School of Medicine, University of Valencia , Valencia, , Spain; Hospital of Jerez, Jerez de la Frontera, and Department of Ophthalmology, University of Cádiz , Cádiz, , Spain; Universitary Hospital Reina Sofia, and Department of Experimental Ophthalmology, University of Murcia , Murcia, , Spain
                Author notes
                [* ]Address correspondence to this author at the Ophthalmic Research Unit “Santiago Grisolía”/FISABIO, University Hospital Dr. Peset. Ave/ Gaspar Aguilar 90; 46017, Valencia, Spain; Tel: + 34 961622497;, Fax: + 34 961622748; E-mail: pinazoduran@ 123456yahoo.es
                Article
                CN-16-903
                10.2174/1570159X15666170705101910
                6120109
                28677495
                8888b7b6-2ece-44bc-826c-d45362d78c96
                © 2018 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 28 February 2017
                : 17 May 2017
                : 22 June 2017
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                glaucoma,oxidative stress,nitrosative stress,antioxidants,essential fatty acids,natural compounds

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