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

Sophie Lavalette 1 William Raoul 1 Marianne Houssier 2 Serge Camelo 2 Olivier Levy 1 Bertrand Calippe 1 Laurent Jonet 2 Francine Behar-Cohen 2 Sylvain Chemtob 3, 4 Xavier Guillonneau 1 Christophe Combadière 5 Florian Sennlaub 1, *
* Auteur correspondant
1 Institut de la Vision
2 CRC (UMR_S 872) - Centre de Recherche des Cordeliers
3 Department of Pediatrics, Ophthalmology and Pharmacology
4 Department of Pharmacology and Therapeutics
5 Immunologie cellulaire et tissulaire
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.
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American Journal of Pathology, American Society for Investigative Pathology, 2011, 178 (5), pp.2416-23. 〈10.1016/j.ajpath.2011.01.013〉
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Sophie Lavalette, William Raoul, Marianne Houssier, Serge Camelo, Olivier Levy, et al.. Interleukin-1β inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration.. American Journal of Pathology, American Society for Investigative Pathology, 2011, 178 (5), pp.2416-23. 〈10.1016/j.ajpath.2011.01.013〉. 〈inserm-00690746〉

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