title: Activation of the Nrf2/HO-1 antioxidant pathway contributes to the protective effects of Lycium barbarum polysaccharides in the rodent retina after ischemia-reperfusion-induced damage.
abstract: Lycium barbarum polysaccharides (LBP), extracts from the wolfberries, are protective to retina after ischemia-reperfusion (I/R). The antioxidant response element (ARE)-mediated antioxidant pathway plays an important role in maintaining the redox status of the retina. Heme oxygenase-1 (HO-1), combined with potent AREs in its promoter, is a highly effective therapeutic target for the protection against neurodegenerative diseases, including I/R-induced retinal damage. The aim of our present study was to investigate whether the protective effect of LBP after I/R damage was mediated via activation of the Nrf2/HO-1-antioxidant pathway in the retina. Retinal I/R was induced by an increase in intraocular pressure to 130 mm Hg for 60 minutes. Prior to the induction of ischemia, rats were orally treated with either vehicle (PBS) or LBP (1 mg/kg) once a day for 1 week. For specific experiments, zinc protoporphyrin (ZnPP, 20 mg/kg), an HO-1 inhibitor, was intraperitoneally administered at 24 h prior to ischemia. The protective effects of LBP were evaluated by quantifying ganglion cell and amacrine cell survival, and by measuring cell apoptosis in the retinal layers. In addition, HO-1 expression was examined using Western blotting and immunofluorescence analyses. Cytosolic and nuclear Nrf2 was measured using immunofluorescent staining. LBP treatment significantly increased Nrf2 nuclear accumulation and HO-1 expression in the retina after I/R injury. Increased apoptosis and a decrease in the number of viable cells were observed in the ganglion cell layer (GCL) and inner nuclear layer (INL) in the I/R retina, which were reversed by LBP treatment. The HO-1 inhibitor, ZnPP, diminished the LBP treatment-induced protective effects in the retina after I/R. Taken together, these results suggested that LBP partially exerted its beneficial neuroprotective effects via the activation of Nrf2 and an increase in HO-1 protein expression.
authors.affiliation: Department of Anatomy/Embryology, School of Basic Medical Sciences, Peking University, Beijing, China ; Key Laboratory on Machine Perception (Ministry of Education), Peking University, Beijing, China ; Key Laboratory for Visual Impairment and Restoration (Ministry of Education), Peking University, Beijing, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Anatomy/Embryology, School of Basic Medical Sciences, Peking University, Beijing, China ; Key Laboratory on Machine Perception (Ministry of Education), Peking University, Beijing, China ; Key Laboratory for Visual Impairment and Restoration (Ministry of Education), Peking University, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Anatomy and Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, Pokfulam, Hong Kong, China ; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Raymond Chuen-Chung
authors.initials: RC
authors.lastname: Chang
authors.affiliation: Department of Anatomy and Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, Pokfulam, Hong Kong, China ; The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China ; GHM Institute of CNS Regeneration, Jinan University, Guangzhou, China.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.affiliation: Department of Ophthalmology, The University of Hong Kong, Pokfulam, Hong Kong, China ; Department of Neurobiology, Department of Medicine, Jules Stein Eye Institute, CURE Digestive Diseases Research Center, David Geffen School of Medicine at Los Angeles, University of California Los Angeles, Los Angeles, California, United States of America ; Veterans Administration, Greater Los Angeles Health System, Los Angeles, California, United States of America.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Brecha
authors.affiliation: Department of Anatomy/Embryology, School of Basic Medical Sciences, Peking University, Beijing, China ; Key Laboratory on Machine Perception (Ministry of Education), Peking University, Beijing, China ; Key Laboratory for Visual Impairment and Restoration (Ministry of Education), Peking University, Beijing, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Pu
mesh_terms: D025042:Amacrine Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D032305:Lycium / Q000737:chemistry*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D021381:Protein Transport; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury; D012160:Retina / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; C500223:lycium barbarum polysaccharide; D051547:Heme Oxygenase-1