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A. Takeda, K. Yamada, M. Nozaki, B. Raisler, R. Albuquerque, J. Baffi, M. Kleinman, B. K. Ambati, J. Ambati; Soluble VEGF Receptor-1 Restores Corneal Avascularity in Corn1 and Pax6+/- Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1733.
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We reported that soluble VEGF receptor-1 (sflt-1) expressed in corneal epithelium binds VEGF-A and maintains corneal avascularity. Although corn1 and Pax6+/– mouse corneas are known to spontaneously vascularize, the underlying mechanisms are unclear. We studied corneal expression of sflt-1 in these mutant mice and in Pax6+/– patients with aniridia associated neovascularization. We also tested the effect of exogenous sflt-1 administration on these mutant corneas.
sflt-1 expression in the corneas of A/J, corn1, Pax6+/+, and Pax6+/– mice was determined by western blotting and in aniridic corneas by immunohistochemistry. sflt-1/Fc or IgG1-Fc protein was injected into the corneas of corn1 and Pax6+/– mice. Cornea flat mounts were stained with CD31-FITC to detect blood vessels.
The avascular corneas of A/J and Pax6+/+ mice expressed sflt-1 whereas corn1 and Pax6+/– corneas did not. Enforced expression of recombinant sflt-1 restored corneal avascularity in these mutant mice. The corneas of patients with aniridia were deficient in sflt-1 compared to normal human corneas.
Dysregulation of sflt-1 is involved in these models of spontaneous corneal neovascularization and administration of sflt-1 can be effective in treating this blinding condition.
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