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To evaluate the effect of topically administered pigment epithelium-derived factor (PEDF) on experimentally induced corneal neovascularization (NV) in a rat model.Corneal chemical cauterization was induced in the left eye by using silver nitrate sticks in 160 anesthetized male Sprague-Dawley rats. The rats were randomly assigned to 4 groups with 40 rats each for topical administration of recombinant PEDF, chloramphenicol, chondroitin sulfate, and normal saline (as control). At different intervals (3, 10, 15, and 30 days) of the treatment, rats were euthanized and the corneas removed for immunohistochemistry and Western blot analyses to measure expression levels of PEDF, vascular endothelial growth factor (VEGF), and CD34, an endothelial maker. The right eyes were used as normal control.There were high levels of PEDF expression and low levels of VEGF and CD34 in the normal cornea. VEGF and CD34 levels were significantly induced by chemical cauterization in the groups treated with chloramphenicol, chondroitin sulfate, and normal saline, demonstrating corneal NV. The VEGF and CD34 levels reached a plateau in the cornea on the 10th day after cauterization and remained at high levels thereafter. In contrast, the PEDF treatment prevented the overexpression of VEGF and CD34 induced by the cauterization.PEDF downregulates VEGF expression and inhibits corneal NV induced by chemical cauterization. The results suggested that PEDF has therapeutic potential for corneal neovascular diseases.