Effect of a topically applied neutralizing antibody against vascular endothelial growth factor on corneal allograft rejection of rat

BACKGROUND: Studies in corneal transplant rejection remain important because acute immunologic rejection continues to be the leading cause of human corneal transplant failure. As the permeability of vessels and the neovascularization induce cells infiltration into the graft, we considered the possibility that vascular endothelial growth factor (VEGF), a potent permeability-increasing factor and angiogenesis-mediating factor, could participate in the immune response. METHODS: As the established corneal transplant model for rejection, the corneal transplant between Lewis and Fisher rats has been reported. First, we evaluated VEGF production in the graft by immunohistochemical method in the animal model. Next, we tried to neutralize the effect of VEGF by topical administration of anti-VEGF antibody. We administered anti-VEGF antibody as eye drops for 10 days just after the transplantation of the established animal corneal transplant model. RESULTS: VEGF was strongly produced from the infiltrative cells into the graft. Anti-VEGF antibody significantly suppressed the acute rejection compared with saline or rabbit IgG. CONCLUSIONS: The inhibition of VEGF by topically applied neutralizing antibody is a new potential therapeutic strategy for the treatment of corneal transplantation.