Hajrasouliha, Amir R.Funaki, ToshinariSadrai, ZahraHattori, TakaakiChauhan, SunilDana, Reza2018-02-082012Hajrasouliha, Amir R., Toshinari Funaki, Zahra Sadrai, Takaaki Hattori, Sunil K. Chauhan, and Reza Dana. 2012. “Vascular Endothelial Growth Factor-C Promotes Alloimmunity by Amplifying Antigen-Presenting Cell Maturation and Lymphangiogenesis.” Investigative Opthalmology & Visual Science 53 (3) (March 9): 1244. doi:10.1167/iovs.11-8668.1552-5783http://nrs.harvard.edu/urn-3:HUL.InstRepos:34814063Purpose. To investigate the role of anti–vascular endothelial growth factor (VEGF)-C therapy in corneal graft survival and concomitant suppression of hem- and lymph-angiogenesis. Methods. Corneal suture model in BALB/c mice was placed and immunohistochemical staining was performed with CD31/PECAM-1 and LYVE-1 to quantify the level of blood and lymphatic vessels. Corneal transplants were done in BALB/c mice from C57BL/6 mice donors; grafts were subsequently scored for opacity. VEGF-C was blocked in the angiogenesis and transplant model using neutralizing monoclonal anti-VEGF-C (VGX-100) by intraperitoneal injection. To determine the function of VEGF-C in maturation of antigen-presenting cells (APCs), bone marrow–derived dendritic cells were generated and matured in the presence or absence of VEGF-C. Results. VEGF-C expression was demonstrated to be markedly upregulated in corneal graft rejection. VEGF-C blockade, through administration of a VEGF-C blocking monoclonal antibody, suppresses corneal angiogenic responses, inhibits trafficking and maturation of APCs, and significantly improves allotransplant survival. Conclusions. These data suggest VEGF-C as a potentially important target in corneal transplant pharmacotherapy and immunobiology.en-USJournal Article2017-06-1920122018-02-0810.1167/iovs.11-8668