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Amir R. Hajrasouliha, Toshinari Funaki, Zahra Sadrai, Takaaki Hattori, Sunil K. Chauhan, Reza Dana; Vascular Endothelial Growth Factor-C Promotes Alloimmunity by Amplifying Antigen-Presenting Cell Maturation and Lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2012;53(3):1244-1250. doi: 10.1167/iovs.11-8668.
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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.
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.
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.
These data suggest VEGF-C as a potentially important target in corneal transplant pharmacotherapy and immunobiology.
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