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Vascular endothelial growth factor (VEGF) is up\u2010regulated by hypoxia in the retina and plays a central role in the development of several types of ocular neovascularization, but the effects of other hypoxia\u2010regulated proteins are less clear. Stromal\u2010de\u2010rived factor\u20101 (SDF\u20101) and its receptor, CXCR4, have hypoxia response elements in the promoter regions of their genes and are increased in hypoxic liver and heart. In this study, we found that SDF\u20101 and CXCR4 are increased in hypoxic retina, with SDF\u20101 localized in glial cells primarily near the surface of the retina and CXCR4 localized in bone marrow\u2010derived cells. Glial cells also expressed CXCR4, which suggested the possibility of autocrine stimulation, but influx of bone marrow\u2010derived cells is the major source of increased levels of CXCR4. High levels of VEGF in the retina in the absence of hypoxia also increased levels of\n                    <jats:italic>Cxcr4<\/jats:italic>\n                    and\n                    <jats:italic>Sdf1<\/jats:italic>\n                    mRNA. CXCR4 antagonists reduced influx of bone marrow\u2010derived cells into ischemic retina and strongly suppressed retinal neovascularization, VEGF\u2010induced subretinal neovascularization, and choroidal neovascularization. These data suggest that SDF\u20101 and CXCR4 contribute to the involvement of bone marrow\u2010derived cells and collaborate with VEGF in the development of several types of ocular neovascularization. They provide new targets for therapeutic intervention that may help to bolster and supplement effects obtained with VEGF antagonists.\u2014Lima e Silva, R., Shen, J., Hackett, S. F., Kachi, S., Akiyama, H., Kiuchi, K., Yokoi, K., Hatara, M. C., Lauer, T., Aslam, S., Gong, Y. Y., Xiao, W\u2010H., Khu, N. H., Thut, C., Campochiaro, P. A. The SDF\u20101\/CXCR4 ligand\/receptor pair is an important contributor to several types of ocular neo\u2010vascularization.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    21, 3219\u20133230 (2007)\n                  <\/jats:p>","DOI":"10.1096\/fj.06-7359com","type":"journal-article","created":{"date-parts":[[2007,5,23]],"date-time":"2007-05-23T21:12:02Z","timestamp":1179954722000},"page":"3219-3230","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["The SDF\u20101\/CXCR4 ligand\/receptor pair is an important contributor to several types of ocular neovascularization"],"prefix":"10.1096","volume":"21","author":[{"given":"Raquel","family":"Lima e Silva","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jikui","family":"Shen","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean F.","family":"Hackett","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Kachi","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Akiyama","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuji","family":"Kiuchi","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutoshi","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Hatara","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lauer","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Aslam","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan Yuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Hong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naw Htee","family":"Khu","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Neuroscience The Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Thut","sequence":"additional","affiliation":[{"name":"Department of Ophthalmics Research Merck &amp; Co. 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