Article: article from journal or magazin.
Interleukin-1β inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration.
American Journal of Pathology
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
The pro-inflammatory cytokine IL-1β has been shown to promote angiogenesis. It can have a neurotoxic or neuroprotective effect. Here, we have studied the expression of IL-1β in vivo and the effect of the IL-1 receptor antagonist on choroidal neovascularization (CNV) and retinal degeneration (RD). IL-1β 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-1β 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-1β significantly increased endothelial cell outgrowth in aortic ring assay independently of vascular endothelial growth factor, suggesting a direct effect of IL-1β on choroidal endothelial cell proliferation. Inhibition of IL-1β 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-1β 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.
Animals, Choroidal Neovascularization/metabolism, Choroidal Neovascularization/prevention & control, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Interleukin-1beta/antagonists & inhibitors, Macrophages/metabolism, Mice, Mice, Inbred C57BL, Nerve Degeneration/metabolism, Nerve Degeneration/pathology, Nerve Regeneration/physiology, Photoreceptor Cells/metabolism, Photoreceptor Cells/pathology, Rats, Rats, Wistar, Retinal Degeneration/metabolism, Retinal Degeneration/prevention & control, Reverse Transcriptase Polymerase Chain Reaction
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