title: Interleukin-1β inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration.
abstract: 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.
authors.affiliation: INSERM, UMR S 872, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lavalette
authors.forename: William
authors.initials: W
authors.lastname: Raoul
authors.forename: Marianne
authors.initials: M
authors.lastname: Houssier
authors.forename: Serge
authors.initials: S
authors.lastname: Camelo
authors.forename: Olivier
authors.initials: O
authors.lastname: Levy
authors.forename: Bertrand
authors.initials: B
authors.lastname: Calippe
authors.forename: Laurent
authors.initials: L
authors.lastname: Jonet
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.forename: Xavier
authors.initials: X
authors.lastname: Guillonneau
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadière
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000517:prevention & control; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology; D010786:Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012162:Retinal Degeneration / Q000378:metabolism* / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053583:Interleukin-1beta