Interleukin (IL)-17A Promotes Angiogenesis in an Experimental Corneal Neovascularization Model

To explore the roles of interleukin (IL)-17A in alkali-induced corneal neovascularization (CRNV).

Induction of CRNV by alkali injury was performed and compared in recombinant mouse IL-17A protein or anti-mouse IL-17A neutralizing antibody (Ab)-treated mice. The expression of IL-17A, IL-17A receptor (IL-17RA), vascular endothelial growth factor (VEGF), IL-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) in burned corneas or other cells was examined by RT-PCR and western blot. The infiltration of macrophages, neutrophils, and c-Kit-positive progenitor cells into burned corneas was detected by flow cytometry (FCM). The Raw264.7 cell line and mouse corneal fibroblasts were stimulated by mouse recombinant IL-17A or anti-mouse IL-17A neutralizing Ab in vitro, and the expression of IL-6 and VEGF in culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA).

The alkali-induced CRNV peaked 2 weeks after the alkali burn. Compared with the vehicle-treated group, mouse recombinant IL-17A administration significantly increased the amount of CRNV, and it decreased in mice treated with neutralizing anti-mouse IL-17A Ab. RT-PCR and western blot confirmed that the IL-17A upregulated intracorneal VEGF, IL-6, IL-8, MCP-1, and phosphorylated focal adhesion kinase (pFAK) expression. FCM revealed that the infiltration of intracorneal progenitor cells, M1 macrophages, and neutrophils was also augmented in IL-17A-treated mice. The ELISA showed that IL-17A markedly induced VEGF and IL-6 expression in the Raw264.7 murine macrophage cell line and in the mouse corneal fibroblasts.

IL-17A-treated mice exhibited enhanced alkali-induced CRNV through enhanced intracorneal progenitor cell and inflammatory cell infiltration, and increased VEGF and IL-6 expression by fibroblasts and macrophages.