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      Lycium barbarum polysaccharide protects ARPE-19 cells against H 2O 2-induced oxidative stress via the Nrf2/HO-1 pathway

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          Abstract

          Age-related macular degeneration (AMD) is a global health problem. Lycium barbarum polysaccharide (LBP), a traditional Chinese herbal medicine, has been proven to be effective against several eye diseases. However, only a few studies have investigated the effectiveness of LBP for AMD. In the present study, the human retinal epithelial cell line, ARPE-19, was pretreated with LBP for 24 h before exposure to H 2O 2 (500 µM). Cell viability was assessed, and a series of oxidative and antioxidant indicators were evaluated to determine the influence of LBP on H 2O 2-triggered oxidative stress. The present study also determined the apoptosis status, as well as the expression levels of apoptotic proteins and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway proteins. The present study aimed to determine the protective role for LBP pretreatment and its underlying molecular mechanism. The results of the present study suggest that pretreatment of ARPE-19 cells with LBP exhibit high efficacy at reducing oxidative damage and inhibiting cell apoptosis. Furthermore, LBP may modulate the expression of proteins involved in the apoptotic pathway and activate the Nrf2 signaling pathway.

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          Most cited references41

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          Nrf2-Keap1 signaling in oxidative and reductive stress

          Nrf2 and its endogenous inhibitor, Keap1, function as a ubiquitous, evolutionarily conserved intracellular defense mechanism to counteract oxidative stress. Sequestered by cytoplasmic Keap1 and targeted to proteasomal degradation in basal conditions, in case of oxidative stress Nrf2 detaches from Keap1 and translocates to the nucleus, where it heterodimerizes with one of the small Maf proteins. The heterodimers recognize the AREs, that are enhancer sequences present in the regulatory regions of Nrf2 target genes, essential for the recruitment of key factors for transcription. In the present review we briefly introduce the Nrf2-Keap1 system and describe Nrf2 functions, illustrate the Nrf2-NF-κB cross-talk, and highlight the effects of the Nrf2-Keap1 system in the physiology and pathophysiology of striated muscle tissue taking into account its role(s) in oxidative stress and reductive stress.
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            Age-related macular degeneration

            Age-related macular degeneration is a leading cause of visual impairment and severe vision loss. Clinically, it is classified as early-stage (medium-sized drusen and retinal pigmentary changes) to late-stage (neovascular and atrophic). Age-related macular degeneration is a multifactorial disorder, with dysregulation in the complement, lipid, angiogenic, inflammatory, and extracellular matrix pathways implicated in its pathogenesis. More than 50 genetic susceptibility loci have been identified, of which the most important are in the CFH and ARMS2 genes. The major non-genetic risk factors are smoking and low dietary intake of antioxidants (zinc and carotenoids). Progression from early-stage to late-stage disease can be slowed with high-dose zinc and antioxidant vitamin supplements. Intravitreal anti-vascular endothelial growth factor therapy (eg, ranibizumab, aflibercept, or bevacizumab) is highly effective at treating neovascular age-related macular degeneration, and has markedly decreased the prevalence of visual impairment in populations worldwide. Currently, no proven therapies for atrophic disease are available, but several agents are being investigated in clinical trials. Future progress is likely to be from improved efforts in prevention and risk-factor modification, personalised medicine targeting specific pathways, newer anti-vascular endothelial growth factor agents or other agents, and regenerative therapies.
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              The retinal pigment epithelium in visual function.

              Located between vessels of the choriocapillaris and light-sensitive outer segments of the photoreceptors, the retinal pigment epithelium (RPE) closely interacts with photoreceptors in the maintenance of visual function. Increasing knowledge of the multiple functions performed by the RPE improved the understanding of many diseases leading to blindness. This review summarizes the current knowledge of RPE functions and describes how failure of these functions causes loss of visual function. Mutations in genes that are expressed in the RPE can lead to photoreceptor degeneration. On the other hand, mutations in genes expressed in photoreceptors can lead to degenerations of the RPE. Thus both tissues can be regarded as a functional unit where both interacting partners depend on each other.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                November 2021
                03 September 2021
                03 September 2021
                : 24
                : 5
                : 769
                Affiliations
                Department of Ophthalmology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116021, P.R. China
                Author notes
                Correspondence to: Dr Qi Zhao, Department of Ophthalmology, The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou, Dalian, Liaoning 116021, P.R. China, E-mail: zhaiqidyey@ 123456163.com
                [*]

                Contributed equally

                Article
                MMR-0-0-12409
                10.3892/mmr.2021.12409
                8436232
                34490478
                403c39d8-ca88-4d68-8a54-2f650fb18c2b
                Copyright: © Liang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 09 May 2021
                : 13 August 2021
                Categories
                Articles

                age-related macular degeneration,oxidative stress,lycium barbarum polysaccharide,retinal pigment epithelium,nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway

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