Soluble vascular endothelial growth factor receptor-1 contributes to the corneal antiangiogenic barrier

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Abstract
Purpose: Pathological neovascularisation within the normally avascular cornea is a serious event that can interfere with normal vision. Upregulation of vascular endothelial growth factor (VEGF) has been associated with neovascularisation in the eye, suggesting that maintaining low levels of VEGF is important for corneal avascularity and intact vision. This study aims to determine the expression profile and possible contribution of sVEGFR-1 to the corneal avascular barrier. Design: Experimental case series investigating VEGF and soluble fms-like tyrosine kinase (sFlt) levels in normal and neovascularised human corneas. Participants: Four normal human corneas, five human corneas with alkali burns, three human corneas with aniridia, one with ocular cicatricial pemphigoid and two with interstitial keratitis were examined. Methods: Western blot and immunohistochemical analyses were performed to determine sFlt and VEGF levels in normal and neovascularised human corneas. Immunoprecipitation was utilised to demonstrate sFlt–VEGF binding. Results: Normal human corneas strongly express sFlt in the corneal epithelium and weakly in the corneal stroma close to the limbus. VEGF is bound by sFlt in the normal human cornea. Neovascularised human corneas have greatly reduced expression of sFlt and significantly less VEGF bound by sFlt. Conclusions: sFlt is highly expressed in the human cornea and normally sequesters VEGF.