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      Effect of Myricetin on Primary Open-angle Glaucoma

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          Abstract

          Background

          Primary open angle glaucoma (POAG) is the most common form of glaucoma, with a multifactorial etiology that results in retinal ganglion cell death and loss of vision. In this study, we assessed the effects of myricetin on the trabecular meshwork cells in POAG.

          Methods

          In the in-vivo model, glaucoma was induced in Sprague-Dawley rats by injecting hyaluronic acid into the anterior chamber of the eye (every week for six-weeks). Treatment group rats were administered myricetin (25, 50 or 100 mg/ kg body weight via oral gavage) each day for of six weeks.

          Results

          POAG TM cells exposed to myricetin (25, 50 or 100 μM) exhibited significantly lowered reactive oxidative species (ROS) levels and lipid peroxidation products. The expressions of transforming growth factors (TGFβ1/β2), vascular endothelial growth factor, and senescence markers (senescence associated-β-galactosidase, cyclin-dependent kinase inhibitors-p16 and p21) were substantially down-regulated in POAG TM cells exposed to myricetin. Myricetin effectively prevented IOP elevation in glaucoma-induced rats and decreased inflammatory cytokines (IL-1α, IL-1β, IL-6, Il-8, TNF-α) in the aqueous humor and POAG TM cells of glaucoma-induced rats.

          Conclusion

          The observations of the study illustrate the protective effects of myricetin in glaucomatous TM cells.

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          Most cited references63

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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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            Myricetin: A Dietary Molecule with Diverse Biological Activities

            Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson’s and Alzheimer’s. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound’s ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities.
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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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                Author and article information

                Journal
                Transl Neurosci
                Transl Neurosci
                tnsci
                tnsci
                Translational Neuroscience
                De Gruyter
                2081-3856
                2081-6936
                12 November 2018
                2018
                : 9
                : 132-141
                Affiliations
                [1 ]deptDepartment of Ophthalmology , Qingdao Municipal Hospital , Qingdao 266011, China
                Author notes
                Article
                tnsci-2018-0020
                10.1515/tnsci-2018-0020
                6234474
                30473883
                d280f742-4974-4edb-8607-a7545a29572e
                © 2018 Qing Yang et al., published by De Gruyter

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

                History
                : 19 March 2018
                : 28 August 2018
                Page count
                Pages: 10
                Categories
                Regular Articles

                glaucoma,inflammatory mediators,myricetin,oxidative stress,senescence markers,trabecular meshwork cells

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