Il-1β Is Produced By Neutrophils In Choroidal Neovascularization And Promotes Vascular Sprouting Independently Of VEGF

Abstract

Purpose: : The pro-inflammatory cytokine interleukin 1 (IL-1β) has been shown to promote subretinal neovascularization in the rat. We have studied the expression and the localization of IL-1β and its receptor (IL-1R) in vivo, the influence of IL-1 on neutrophil and macrophage recruitment and the effect of VEGF blockage on IL1 induced vascular sprouting in the aortic ring assay

Methods: : C57B6j mice were submitted to laser induced injury. IL-1β and IL-1R expression was studied by rtRCR and immunohistochemistry. Neutrophil (anti-Ly6G) and macrophage (anti-Iba1) recruitment (10h and d3) were quantified on stained choroidal flatmount from controls and IL-1Ra treated animals. Vascular sprouting was analyzed in IL-1β in the presence or absence of soluble VEGFR1

Results: : IL-1β mRNA increased robustly (25 fold 1 to 20h) after laser injury, while there was only a trend of VEGF mRNA increase (2,5 fold at 1h) that did not reach statistical significance. IL-1β mainly located to infiltrating neutrophils but not macrophages and IL-1R was expressed on choroidal neovascularization (CNV). IL-1Ra treatment increased neutrophil recruitment at 10h, had no effect on macrophage recruitment and inhibited CNV at d14. IL-1 increased vascular sprouting in aortic rings that was inhibited by IL-1RA but not sVEGFR1

Conclusions: : Infiltrating neutrophils are the major source of IL-1β in laser-induced CNV. IL-1β inhibits further neutrophil recruitment but does not affect macrophage recruitment. IL-1R is mainly expressed on vascular endothelium of the CNV in vivo and IL-1β promotes vascular sprouting independently of VEGF in vitro. IL1 inhibition might represent a valuable alternative to VEGF inhibition in the control of CNV in AMD

Keywords: age-related macular degeneration • choroid: neovascularization • inflammation