SKLB1002, a potent inhibitor of VEGF receptor 2 signaling, inhibits endothelial angiogenic function in vitro and ocular angiogenesis in vivo.

Ocular angiogenesis is a major cause of severe vision loss, which can affect several parts of the eye, including the retina, choroid and cornea. Vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors have demonstrated great potential for treating ocular angiogenesis and SKLB1002 is a potent inhibitor of VEGF receptor 2 signaling. The present study investigated the effects of SKLB1002 administration on ocular angiogenesis. SKLB1002 administration did not show obvious cytotoxicity and tissue toxicity at the tested concentrations. In an alkali­burn corneal model, SKLB1002 administration significantly decreased the mean length and number of new corneal blood vessels. SKLB1002 administration significantly reduced endothelial cell proliferation, migration and tube formation in vitro. Mechanistically, SKLB1002 inhibited endothelial angiogenic functions by blocking the phosphorylation of ERK1/2, JNK and p38. Thus, selective inhibition of VEGFR­2 through SKLB1002 administration is a promising therapy for ocular angiogenesis.

Osthole: A Traditional Chinese Medicine for Ocular Anti-Angiogenic Therapy.

PURPOSE: Osthole is an agent isolated from Cnidium monnieri (L.) Cusson and has been used to treat several disorders. Corneal neovascularization is a sight-threatening condition associated with several inflammatory or infectious ocular disorders. In this study, we investigated the anti-angiogenic effects of osthole on corneal neovascularization and the underlying mechanism. METHODS: MTT assay, HE staining, and calcein-AM/propidium iodide staining was conducted to detect the toxicity of osthole in vitro and in vivo. Corneal neovascularization of ICR mice was induced by alkali burn and observed by a slit lamp microscopy on day 7 after alkali injury. EdU assay, Ki67 immunofluorescence assay, Transwell migration assay, and Matrigel assay were conducted to investigate the role of osthole in endothelial angiogenic effects in vitro. Western blots were conducted to investigate the anti-angiogenic mechanism of osthole in corneal neovascularization. RESULTS: Administration of osthole ranging from 0.05 to 25 µM had no detectable cytotoxicity or tissue toxicity in vivo and in vitro. Topical administration of osthole inhibited corneal neovascularization induced by alkali burn. Osthole decreased the proliferation, migration, and tube-formation of endothelial cells induced by VEGF. Osthole inhibited endothelial angiogenic functions through blocking the phosphorylation of ERK1/2, JNK, and p38. CONCLUSION: Our study provides evidence that osthole is a promising drug for the treatment of corneal neovascularization.