Abstract
Purpose: :
The pro-inflammatory cytokine interleukin 1 (IL1) has been shown to promote subretinal neovascularization in the rat (Olsen et al. 2009). Here we have studied the expression of IL1 and its natural inhibitor Interleukin 1 receptor antagonist (IL1RA) in vivo and the effect of aditional IL1RA substitution on macrophage recruitment and choroidal neovascularization in the mouse. Furthermore we studied the effect of IL1 on endothelial cell proliferation in aortic rings.
Methods: :
Wild type mice c57B6j were submitted to laser induced injury. IL1β, iL1ra expression was analyzed in the choroid at different time points by real time rtPCR. Macrophage recruitment (at d4, anti-IBA1) and choroidal neovascularization (at d14, anti-CD102) were quantified on stained choroidal flatmounts from IL1RA treated animals and controls. The influence of IL1 on endothelial cell proliferation was studied using the aortic ring assay.
Results: :
IL1 and IL1RA mRNA increases 25 fold and 4 fold respectively 6h after laser injury. IL1RA treatment significantly inhibited choroidal neovascularization at d14, but not macrophage recruitment to the injury site at d4. IL-1 significantly increases endothelial cell outgrowth in aortic rings.
Conclusions: :
Although both, IL1 and IL1RA are induced after laser injury, IL1 induction greatly surpasses its antagonist induction, suggesting the presence of uninhibited IL1 after laser-induced injury. Indeed, IL1RA substitution very significantly inhibits neovascularization. The lack of inhibition of macrophage recruitment in IL1RA treated animals and the increased vascular endothelial proliferation in IL1 stimulated aortic rings suggest a direct effect of IL1 on choroidal endothelial cell proliferation. IL1 inhibition might represent a valuable alternative to VEGF inhibition in the control of choroidal neovascularization in AMD.
Keywords: age-related macular degeneration • cytokines/chemokines • choroid: neovascularization