The IL-23/IL-17 axis promotes the formation of retinal neovascularization by activating the NLRP3 inflammasome in macrophages in an experimental retinopathy mouse model.

Abstract

Retinal neovascularization (RNV), a pathological process shared among diabetic retinopathy, retinopathy of prematurity and other retinopathies, has been widely studied, but the mechanism remains unclear. In this study, the mechanism by which the interleukin (IL)-23/IL-17 axis regulates RNV in oxygen-induced retinopathy (OIR) model mice and in cell experiments in vitro was characterized. In the retinas of OIR mice, IL-23/IL-17 axis activation was increased and regulated RNV formation, and this effect was accompanied by increased macrophage recruitment and nucleotide-binding domain leucine-rich repeat and pyrin domain containing receptor 3 (NLRP3) inflammasome activation. Moreover, inhibiting the IL-23/IL-17 axis reduced the number of macrophage and the expression and activation of NLRP3 inflammasome. On the other hand, recombinant (r) IL-23p19 and rIL-17A promoted the expression and activation of NLRP3 inflammasome, and the proliferation and migration of macrophages. Furthermore, macrophage elimination decreased the activation of IL-23/IL-17 axis and the expression and activation of NLRP3 inflammasome. In summary, our experiments showed that the IL-23/IL-17 axis promoted the formation of RNV by activating the NLRP3 inflammasome in retinal macrophages of an OIR mouse model.