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

Am J Pathol. 2011 May;178(5):2416-23. doi: 10.1016/j.ajpath.2011.01.013.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Interleukin-1beta