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Mechanisms of retinal angiogenesis, particularly the signaling pathways independent of VEGF, remain elusive. The goals of our study were to explore TLR4\u2010mediated signaling pathways in human retinal microvascular endothelial cells (HRMECs) and to examine the effects of TLR4 antagonists in models of oxygen\u2010induced retinopathy (OIR). Our results show that intravitreal injection of the TLR4 antagonist TAK\u2010242 reduced areas of nonperfusion, inhibited aberrant angiogenesis, and improved vascular density in the retina of OIR mice. The effects were further potentiated by the anti\u2010VEGF antibody ranibizumab. In cultured HRMECs, the TLR4 agonist LPS up\u2010regulated TLR4\/MAPKK kinase kinase 4 (MAP4K4) signaling, and promoted cell proliferation and migration, and reduced barrier functions of the cells. Down\u2010regulation of MAP4K4 in HRMECs abolished the proangiogenic effects by LPS. Our data suggest that the TLR4\u2013MAP4K4 pathway can regulate retinal neovascularization\n                    <jats:italic>via<\/jats:italic>\n                    mechanisms independent of VEGF.\u2014Chen, W., Zhang, J., Zhang, P., Hu, F., Jiang, T., Gu, J., Chang, Q. Role of TLR4\u2010MAP4K4 signaling pathway in models of oxygen\u2010induced retinopathy. FASEB J. 33, 3451\u20133464 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201801086rr","type":"journal-article","created":{"date-parts":[[2018,11,26]],"date-time":"2018-11-26T15:19:11Z","timestamp":1543245551000},"page":"3451-3464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Role of TLR4\u2010MAP4K4 signaling pathway in models of oxygen\u2010induced retinopathy"],"prefix":"10.1096","volume":"33","author":[{"given":"Wenwen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye and Ear, Nose and Throat Hospital  Shanghai China"},{"name":"Key Laboratory of Myopia of National Health Commission Fudan University  Shanghai China"},{"name":"Key Laboratory of Myopia Chinese Academy of Medical Sciences  Shanghai China"},{"name":"Key Laboratory of Visual Impairment and Restoration of Shanghai  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye and Ear, Nose and Throat Hospital  Shanghai China"},{"name":"Key Laboratory of Myopia of National Health Commission Fudan University  Shanghai China"},{"name":"Key Laboratory of Myopia Chinese Academy of Medical Sciences  Shanghai China"},{"name":"Key Laboratory of Visual Impairment and Restoration of Shanghai  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye and Ear, Nose and Throat Hospital  Shanghai China"},{"name":"Key Laboratory of Myopia of National Health Commission Fudan University  Shanghai China"},{"name":"Key Laboratory of Myopia Chinese Academy of Medical Sciences  Shanghai China"},{"name":"Key Laboratory of Visual Impairment and Restoration of Shanghai  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye and Ear, Nose and Throat Hospital  Shanghai China"},{"name":"Key Laboratory of Myopia of National Health Commission Fudan University  Shanghai China"},{"name":"Key Laboratory of Myopia Chinese Academy of Medical Sciences  Shanghai China"},{"name":"Key Laboratory of Visual Impairment and Restoration of Shanghai  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye and Ear, Nose and Throat Hospital  Shanghai China"},{"name":"Key Laboratory of Myopia of National Health Commission Fudan University  Shanghai China"},{"name":"Key Laboratory of Myopia Chinese Academy of Medical Sciences  Shanghai China"},{"name":"Key Laboratory of Visual Impairment and Restoration of Shanghai  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junxiang","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye and Ear, Nose and Throat Hospital  Shanghai China"},{"name":"Key Laboratory of Myopia of National Health Commission Fudan University  Shanghai China"},{"name":"Key Laboratory of Myopia Chinese Academy of Medical Sciences  Shanghai China"},{"name":"Key Laboratory of Visual Impairment and Restoration of Shanghai  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Eye and Ear, Nose and Throat Hospital  Shanghai China"},{"name":"Key Laboratory of Myopia of National Health Commission Fudan University  Shanghai China"},{"name":"Key Laboratory of Myopia Chinese Academy of Medical Sciences  Shanghai China"},{"name":"Key Laboratory of Visual Impairment and Restoration of Shanghai  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2147\/EB.S105319","article-title":"Advances in diagnosis, clinical care, research, and treatment in retinopathy of prematurity","volume":"8","author":"Hartnett M. 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