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Publication : Interleukin-1β inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration.

First Author  Lavalette S Year  2011
Journal  Am J Pathol Volume  178
Issue  5 Pages  2416-23
PubMed ID  21514452 Mgi Jnum  J:171577
Mgi Id  MGI:4950595 Doi  10.1016/j.ajpath.2011.01.013
Citation  Lavalette S, et al. (2011) Interleukin-1beta inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration. Am J Pathol 178(5):2416-23
abstractText  The pro-inflammatory cytokine IL-1beta has been shown to promote angiogenesis. It can have a neurotoxic or neuroprotective effect. Here, we have studied the expression of IL-1beta in vivo and the effect of the IL-1 receptor antagonist on choroidal neovascularization (CNV) and retinal degeneration (RD). IL-1beta expression significantly increased after laser injury (real time PCR) in C57BL/6 mice, in the C57BL/6 Cx3cr1(-/-) model of age-related macular degeneration (enzyme-linked immunoabsorbent assay), and in albino Wistar rats and albino BALB Cx3cr1(+/+) and Cx3cr1(-/-) mice (enzyme-linked immunoabsorbent assay) after light injury. IL-1beta was localized to Ly6G-positive, Iba1-negative infiltrating neutrophils in laser-induced CNV as determined by IHC. IL-1 receptor antagonist treatment significantly inhibited CNV but did not affect Iba1-positive macrophage recruitment to the injury site. IL-1beta significantly increased endothelial cell outgrowth in aortic ring assay independently of vascular endothelial growth factor, suggesting a direct effect of IL-1beta on choroidal endothelial cell proliferation. Inhibition of IL-1beta in light- and laser-induced RD models did not alter photoreceptor degeneration in Wistar rats, C57BL/6 mice, or RD-prone Cx3cr1(-/-) mice. Our results suggest that IL-1beta inhibition might represent a valuable and safe alternative to inhibition of vascular endothelial growth factor in the control of CNV in the context of concomitant photoreceptor degeneration as observed in age-related macular degeneration.
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