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When neonatal mice were subjected to ischemia-induced retinopathy, pathological retinal neovascularization during ischemia was exacerbated in adiponectin-knockout (APN-KO) mice compared with wild-type mice (neovascular area: 17.0\u00b11.0% versus 11.7\u00b10.6%, respectively). APN-KO mice also exhibited increased leukocyte adhesion (2.3\u00b10.4-fold) and tumor necrosis factor (TNF)-\u03b1 expression (2.6\u00b10.2-fold) in hypoxic retina. Adenovirus-mediated overexpression of adiponectin attenuated hypoxia-induced pathological retinal neovascularization by 35% in wild-type mice and by 40% in APN-KO mice and leukostasis by 64% in wild-type mice and by 75% in APN-KO mice, which were associated with reduced TNF-\u03b1 production. TNF-\u03b1 blockade diminished the enhanced pathological neovascularization in APN-KO mice by 34%, and the inhibitory effects of adiponectin overexpression on retinal neovascularization and leukocyte adhesion were abolished in mice lacking TNF-\u03b1. These data provide evidence that adiponectin protects against retinal vessel injury following pathological stimuli through modulation of TNF-\u03b1 inflammatory responses.<\/jats:p>","DOI":"10.1161\/circresaha.109.194506","type":"journal-article","created":{"date-parts":[[2009,4,3]],"date-time":"2009-04-03T01:49:51Z","timestamp":1238723391000},"page":"1058-1065","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Adiponectin Suppresses Pathological Microvessel Formation in Retina Through Modulation of Tumor Necrosis Factor-\u03b1 Expression"],"prefix":"10.1161","volume":"104","author":[{"given":"Akiko","family":"Higuchi","sequence":"first","affiliation":[{"name":"From Molecular Cardiology\/Whitaker Cardiovascular Institute (A.H., K.O., K.W., N.O.), Boston University School of Medicine, Mass; and Department of Metabolic Medicine (S.K.), Graduate School of Medicine, Osaka University, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Ohashi","sequence":"additional","affiliation":[{"name":"From Molecular Cardiology\/Whitaker Cardiovascular Institute (A.H., K.O., K.W., N.O.), Boston University School of Medicine, Mass; and Department of Metabolic Medicine (S.K.), Graduate School of Medicine, Osaka University, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kihara","sequence":"additional","affiliation":[{"name":"From Molecular Cardiology\/Whitaker Cardiovascular Institute (A.H., K.O., K.W., N.O.), Boston University School of Medicine, Mass; and Department of Metabolic Medicine (S.K.), Graduate School of Medicine, Osaka University, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Walsh","sequence":"additional","affiliation":[{"name":"From Molecular Cardiology\/Whitaker Cardiovascular Institute (A.H., K.O., K.W., N.O.), Boston University School of Medicine, Mass; and Department of Metabolic Medicine (S.K.), Graduate School of Medicine, Osaka University, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Ouchi","sequence":"additional","affiliation":[{"name":"From Molecular Cardiology\/Whitaker Cardiovascular Institute (A.H., K.O., K.W., N.O.), Boston University School of Medicine, Mass; and Department of Metabolic Medicine (S.K.), Graduate School of Medicine, Osaka University, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.20.2579"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04482"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-18601"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-200312000-00003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.45.26746"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1295"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm724"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200251200"},{"key":"e_1_3_3_9_2","first-page":"1645","volume":"118","year":"2008","unstructured":"Sharma K, Ramachandrarao S, Qiu G, Usui HK, Zhu Y, Dunn SR, Ouedraogo R, Hough K, McCue P, Chan L, Falkner B, Goldstein BJ. 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