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      Echinacoside protects retinal ganglion cells from ischemia/reperfusion-induced injury in the rat retina

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      1 , 1 , 2 , 1 , , 1 ,
      Molecular Vision
      Molecular Vision

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          Abstract

          Objective

          To investigate whether echinacoside (ECH) protects the retina against ischemia/reperfusion (I/R) injury and the underlying mechanisms.

          Methods

          Adult male Wistar rats were randomly divided into four groups: sham, sham plus ECH, I/R plus vehicle, and I/R plus ECH. Before the retinal I/R injury produced by high intraocular pressure (HOP), ECH was administered (20 mg/kg daily) for 7 days. The level of retinal cell damage was evaluated using Fluoro-Gold (FG) retrograde labeling and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) analysis 7 days after I/R. Optic nerve histology was analyzed with transmission electron microscopy. Levels of retinal malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were determined. The expression of apoptosis-associated factors (Apaf-1, Parp, and Bad) were analyzed with western blotting and quantitative real-time PCR (qPCR). The production of proinflammatory cytokines (tumor necrosis factor-α [TNFα], interleukin-1 beta [IL-1β], and IL-6) was analyzed with enzyme-linked immunosorbent assay (ELISA) 7 days after the I/R injury as well.

          Results

          The administration of ECH not only preserved retinal morphology but also attenuated retinal inflammation and apoptosis at 7 days after the I/R injury and decreased I/R-induced oxidative stress in the retina statistically significantly.

          Conclusions

          ECH protected against I/R-induced retinal injury, via activation of antioxidant enzymes and suppression of inflammation. Therefore, ECH could be a potential therapeutic candidate for the treatment and management of I/R retinal diseases.

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          Most cited references38

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          A simple method for clinical assay of superoxide dismutase.

          This assay for superoxide dismutase (SOD, EC 1.15.1.1) activity involves inhibition of nitroblue tetrazolium reduction, with xanthine-xanthine oxidase used as a superoxide generator. By using a reaction terminator, we can determine 40 samples within 55 min. One unit of activity of pure bovine liver Cu,ZnSOD and chicken liver MnSOD was expressed by 30 ng and 500 ng of protein, respectively. The mean concentrations of Cu,ZnSOD as measured by this method in blood from normal adults were 242 (SEM 4) mg/L in erythrocytes, 548 (SEM 20) micrograms/L in serum, and 173 (SEM 11) micrograms/L in plasma. The Cu,ZnSOD concentrations in serum and plasma of patients with cancer of the large intestine tended to be less and greater than these values, respectively, but not statistically significantly so.
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            Malondialdehyde determination as index of lipid peroxidation.

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              Retinal ischemia: mechanisms of damage and potential therapeutic strategies.

              Retinal ischemia is a common cause of visual impairment and blindness. At the cellular level, ischemic retinal injury consists of a self-reinforcing destructive cascade involving neuronal depolarisation, calcium influx and oxidative stress initiated by energy failure and increased glutamatergic stimulation. There is a cell-specific sensitivity to ischemic injury which may reflect variability in the balance of excitatory and inhibitory neurotransmitter receptors on a given cell. A number of animal models and analytical techniques have been used to study retinal ischemia, and an increasing number of treatments have been shown to interrupt the "ischemic cascade" and attenuate the detrimental effects of retinal ischemia. Thus far, however, success in the laboratory has not been translated to the clinic. Difficulties with the route of administration, dosage, and adverse effects may render certain experimental treatments clinically unusable. Furthermore, neuroprotection-based treatment strategies for stroke have so far been disappointing. However, compared to the brain, the retina exhibits a remarkable natural resistance to ischemic injury, which may reflect its peculiar metabolism and unique environment. Given the increasing understanding of the events involved in ischemic neuronal injury it is hoped that clinically effective treatments for retinal ischemia will soon be available.
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                Author and article information

                Journal
                Mol Vis
                Mol. Vis
                MV
                Molecular Vision
                Molecular Vision
                1090-0535
                2018
                25 November 2018
                : 24
                : 746-758
                Affiliations
                [1 ]Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
                [2 ]Department of Ophthalmology, First Affiliated Hospital of Dalian Medical University, DaLian, Liaoning Province, China
                Author notes

                The first three authors contributed equally to this paper.

                Correspondence to: Zhenzhen Zhang, Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, No 639 ZhiZaoJu Road, Shanghai 200011, China; Phone:+86-21-23271699; FAX: +86-02163136856; email: zzz1982.happy@ 123456163.com , jannetlee1300@ 123456163.com
                Article
                63 2018MOLVIS0090
                6279312
                30581281
                e43876f2-9aad-4433-8fd6-a63e4a4580cd
                Copyright © 2018 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, used for non-commercial purposes, and is not altered or transformed.

                History
                : 31 March 2018
                : 23 November 2018
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                Vision sciences
                Vision sciences

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