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Inhibition was proportional to dose and systemic delivery\n of recombinant protein at daily doses as low as 2.2 mg\/kg could\n prevent aberrant endothelial cells from crossing the inner limiting\n membrane. PEDF appeared to inhibit angiogenesis by causing\n apoptosis of activated endothelial cells, because it induced\n apoptosis in cultured endothelial cells and an 8-fold increase\n in apoptotic endothelial cells could be detected\n                    <jats:italic>in\n situ<\/jats:italic>\n                    when the ischemic retinas of PEDF-treated animals were\n compared with vehicle-treated controls. The ability of low doses of\n PEDF to curtail aberrant growth of ocular endothelial cells without\n overt harm to retinal morphology suggests that this natural protein may\n be beneficial in the treatment of a variety of retinal vasculopathies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.031252398","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"2593-2597","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":261,"title":["Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor"],"prefix":"10.1073","volume":"98","author":[{"given":"Veronica","family":"Stellmach","sequence":"first","affiliation":[{"name":"Department of Microbiology\u2013Immunology and Robert H. Lurie\r Comprehensive Cancer Center, Veterans Affairs Chicago\r Health Care System\u2013Lakeside Division, and Children's\r Memorial Institute for Education and Research and Department of\r Pathology, Northwestern University Medical School, 320 East\r Superior Street, Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Microbiology\u2013Immunology and Robert H. Lurie\r Comprehensive Cancer Center, Veterans Affairs Chicago\r Health Care System\u2013Lakeside Division, and Children's\r Memorial Institute for Education and Research and Department of\r Pathology, Northwestern University Medical School, 320 East\r Superior Street, Chicago, IL 60611"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology\u2013Immunology and Robert H. 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