**Role of Corneal Neovascularization in Corneal Graft Rejection**

Corneal neovascularization remains a significant risk factor for corneal graft rejection and subsequent graft failure after penetrating keratoplasty. The collaborative corneal transplantation study1 identified, in addition to several other factors, the extent of stromal vessels (quadrants) as a serious risk factor for corneal graft failure. During corneal neovascularization, an upregulation of angiogenic factors is seen in association with down regulation of antiangiogenic molecules. Studies in human and rat models have found vascular endothelial growth factor (VEGF) to be up regulated in inflamed and vascularized cornea .2 In a mouse model, it was observed that corneal avascularity during development is redundantly regulated. Lack of the antiangiogenic factors thrombospondin (TSP)-1 and/or - 2 resulted in no spontaneous corneal angiogenesis. By contrast, TSP-1, more than TSP-2, helped to suppress inflammation-induced corneal angiogenesis postnatally, implying that angiogenic privilege in the cornea is actively maintained .3 Bachmann et al4 in a mouse model found that neutralization of VEGF-A after high-risk corneal transplantation effectively inhibited postoperative hemangiogenesis, lymphangiogenesis, and recruitment of antigen-presenting cells, thereby improving corneal graft survival.

Vascular endothelial growth factor promotes several steps of angiogenesis, including proteolytic activities, endothelial cell proliferation, migration, and capillary tube formation . 5 Topical or systemic application of bevacizumab inhibited both inflammation-induced angiogenesis and lymphangiogenesis in the cornea. This finding suggestes an important role of VEGF-A in corneal lymphangiogenesis and bevacizumab may be useful in preventing immune rejections after penetrating keratoplasty.
