Cursiefen, ClausCao, JingtaiChen, LuLiu, YingMaruyama, KazuichiJackson, DavidKruse, Friedrich E.Wiegand, Stanley J.Dana, RezaStreilein, J. Wayne2017-11-272004Cursiefen,Claus, Jingtai Cao, Lu Chen, Ying Liu, Kazuichi Maruyama, David Jackson, Friedrich E. Kruse, Stanley J. Wiegand, M. Reza Dana, and J. Wayne Streilein. 2004. “Inhibition of Hemangiogenesis and LymphangiogenesisafterNormal-Risk Corneal Transplantation by Neutralizing VEGF Promotes Graft Survival.” Investigative Opthalmology & Visual Science 45 (8) (August 1): 2666. doi:10.1167/iovs.03-1380.1552-5783http://nrs.harvard.edu/urn-3:HUL.InstRepos:34388126purpose. To evaluate the occurrence and time course of hem- and lymphangiogenesis after normal-risk corneal transplantation in the mouse model and to test whether pharmacologic strategies inhibiting both processes improve long-term graft survival. methods. Normal-risk allogeneic (C57BL/6 to BALB/c) and syngeneic (BALB/c to BALB/c) corneal transplantations were performed and occurrence and time course of hem- and lymphangiogenesis after keratoplasty was observed, by using double immunofluorescence of corneal flatmounts (with CD31 as a panendothelial and LYVE-1 as a lymphatic vascular endothelium–specific marker). A molecular trap designed to eliminate VEGF-A (VEGF TrapR1R2; 12.5 mg/kg) was tested for its ability to inhibit both processes after keratoplasty and to promote long-term graft survival (intraperitoneal injections on the day of surgery and 3, 7, and 14 days later). results. No blood or lymph vessels were detectable immediately after normal-risk transplantation in either donor or host cornea, but hem- and lymphangiogenesis were clearly visible at day 3 after transplantation. Both vessel types reached donor tissue at 1 week after allografting and similarly after syngeneic grafting. Early postoperative trapping of VEGF-A significantly reduced both hem- and lymphangiogenesis and significantly improved long-term graft survival (78% vs. 40%; P < 0.05). conclusions. There is concurrent, VEGF-A-dependent hem- and lymphangiogenesis after normal-risk keratoplasty within the preoperatively avascular recipient bed. Inhibition of hem- and lymphangiogenesis (afferent and efferent arm of an immune response) after normal-risk corneal transplantation improves long-term graft survival, establishing early postoperative hem- and lymphangiogenesis as novel risk factors for graft rejection even in low-risk eyes.en-USJournal Article2017-06-1820042017-11-2710.1167/iovs.03-1380