title: Sulforaphane protects rodent retinas against ischemia-reperfusion injury through the activation of the Nrf2/HO-1 antioxidant pathway.
abstract: Retinal ischemia-reperfusion (I/R) injury induces oxidative stress, leukocyte infiltration, and neuronal cell death. Sulforaphane (SF), which can be obtained in cruciferous vegetables such as broccoli, exerts protective effects in response to oxidative stress in various tissues. These effects can be initiated through nuclear factor E2-related factor 2 (Nrf2)-mediated induction of heme oxygenase-1 (HO-1). This investigation was designed to elucidate the neural protective mechanisms of SF in the retinal I/R rat model. Animals were intraperitoneally (i.p.) injected with SF (12.5 mg/kg) or vehicle (corn oil) once a day for 7 consecutive days. Then, retinal I/R was made by elevating the intraocular pressure (IOP) to 130 mmHg for 1 h. To determine if HO-1 was involved in the Nrf2 antioxidant pathway, rats were subjected to protoporphyrin IX zinc (II) (ZnPP, 30 mg/kg, i.p.) treatments at 24 h before retinal ischemia. The neuroprotective effects of SF were assessed by determining the morphology of the retina, counting the infiltrating inflammatory cells and the surviving retinal ganglion cells (RGCs) and amacrine cells, and measuring apoptosis in the retinal layers. The expression of Nrf2 and HO-1 was studied by immunofluorescence analysis and western blotting. I/R induced a marked increase of ROS generation, caused pronounced inflammation, increased the apoptosis of RGCs and amacrine cells and caused the thinning of the inner retinal layer (IRL), and these effects were diminished or abolished by SF pretreatment. Meanwhile, SF pretreatment significantly elevated the nuclear accumulation of Nrf2 and the level of HO-1 expression in the I/R retinas; however, ZnPP reversed the protective effects of SF on I/R retinas. Together, we offer direct evidence that SF had protective effects on I/R retinas, which could be attributed, at least in part, to the activation of the Nrf2/HO-1 antioxidant pathway.
authors.affiliation: Neuroscience Research Institute, Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China; Department of Anatomy/Embryology, School of Basic Medical Sciences, Peking University, Beijing, China; Department of Physiology, Binzhou Medical College, Yantai, Shandong, 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/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: Ruixing
authors.initials: R
authors.lastname: Liu
authors.affiliation: 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: Neuroscience Research Institute, Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Albert Cheung Hoi
authors.initials: AC
authors.lastname: Yu
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 / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007249:Inflammation / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D007429:Intraocular Pressure / Q000187:drug effects; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013454:Sulfoxides; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D051547:Heme Oxygenase-1; C016766:sulforaphane