PURPOSE: 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.
PURPOSE: 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.
Authors: Keryn A Williams; Adrian J Esterman; Christine Bartlett; Helene Holland; Ngaere B Hornsby; Douglas J Coster Journal: Transplantation Date: 2006-03-27 Impact factor: 4.939
Authors: A Lymboussaki; T A Partanen; B Olofsson; J Thomas-Crusells; C D Fletcher; R M de Waal; A Kaipainen; K Alitalo Journal: Am J Pathol Date: 1998-08 Impact factor: 4.307
Authors: Steven A Stacker; Steven P Williams; Tara Karnezis; Ramin Shayan; Stephen B Fox; Marc G Achen Journal: Nat Rev Cancer Date: 2014-03 Impact factor: 60.716
Authors: Francisco Amparo; Zahra Sadrai; Yiping Jin; Belen Alfonso-Bartolozzi; Haobing Wang; Hasanain Shikari; Joseph B Ciolino; James Chodosh; Ula Jurkunas; Debra A Schaumberg; Reza Dana Journal: Invest Ophthalmol Vis Sci Date: 2013-01-17 Impact factor: 4.799