Blockade of angiopoietin-2/Tie2 signaling pathway specifically promotes inflammation-induced angiogenesis in mouse cornea

Abstract

AIM: To investigate angiopoietin-2 (Ang-2)/Tie2 signaling pathway involving in inflammatory angiogenesis. METHODS: Three interrupted 11-0 nylon sutures were placed into the corneal stroma of BALB/c mice (6wk old) to induce inflammatory neovascularization. Expression of Ang-2 and Tie2 protein on neovascularization were examined by immunofluorescence. The dynamic expression of Ang-2 mRNA on neovascularization was examined by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Finally, the mouse model of suture-induced corneal neovascularization was used to assess the role of Ang-2/Tie2 signaling pathway in inflammatory angiogenesis by systemic application of L1-10, an Ang-2 specific inhibitor. Mouse corneal hemangiogenesis were evaluated by whole mount immunofluorescence. RESULTS: Both Ang-2 and Tie2 were expressed on newly generated blood vessels in inflammatory cornea. Ang-2 expression was gradually upregulated around 2wk following injury, which was concurrent with an increased number of blood vessels. Blockade of Ang-2/Tie2 signaling pathway obviously promoted angiogenesis in inflammatory cornea. CONCLUSION: Ang-2/Tie2 signaling pathway seems to play an important role during angiogenesis in inflammatory cornea. This may open new therapeutic applications in pathological processes such as corneal graft survival, wound healing and carcinogenesis.