therapeutic effects of topical netrin4 inhibits corneal neovascularization in alkaliburn rats netrins are secreted molecules involved in axon guidance and angiogenesis however the role of netrins in the vasculature remains unclear netrin4 and netrin1 have been found to be either pro or antiangiogenic factors previously we found that netrin1 acts as an antiangiogenic factor in rats by inhibiting alkali burninduced corneal neovascularization here we further investigate the effects of netrin4 another member of the same netrin family on neovascularization in vitro and in vivo we found that netrin4 functions similarly as netrin1 in angiogenesis in vitro angiogenesis assay shows that netrin4 affected human umbilical vein endothelial cell huvec tube formation viability and proliferation apoptosis migration and invasion in a dosedependent manner netrin4 was topically applied in vivo to alkaliburned rat corneas on day 0 immediately after injury andor day 10 postinjury netrin4 subsequently suppressed and reversed corneal neovascularization netrin4 inhibited corneal epithelial and stromal cell apoptosis inhibited vascular endothelial growth factor vegf but promoted pigment epitheliumderived factor pedf expression decreased nkkb p65 expression and inhibits neutrophil and macrophage infiltration these results indicate that netrin4 shed new light on its potential roles in treatmenting for angiogenic diseases that affect the ocular surface as well as other tissues