Interleukin-1β inhibition prevents choroidal neovascularization and does not exacerbate photoreceptor degeneration
Autor: | Christophe Combadière, William Raoul, Bertrand Calippe, Laurent Jonet, Serge Camelo, Olivier Levy, Florian Sennlaub, Xavier Guillonneau, Sophie Lavalette, Marianne Houssier, Sylvain Chemtob, Francine Behar-Cohen |
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Přispěvatelé: | Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Pediatrics, Ophthalmology and Pharmacology, Hôpital Sainte-Justine, Department of Pharmacology and Therapeutics [Montréal], McGill University = Université McGill [Montréal, Canada], Immunologie cellulaire et tissulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR 'blanc' (AO5120DD), ANR 'Maladies Neurologiques et Maladies Psychiatriques' (R08098DS), ANR 'Genopat' (R09099DS), European Grant 'Innochem' (LSHB-CT-2005-518167), ERC starting Grant (ERC-2007 St.G. 210345), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Pharmacology and Therapeutics, McGill University, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Sainte Justine [Montréal], Raoul, William |
Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Retinal degeneration
MESH: Nerve Regeneration genetic structures [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Angiogenesis medicine.medical_treatment Interleukin-1beta MESH: Nerve Degeneration chemistry.chemical_compound Mice 0302 clinical medicine MESH: Interleukin-1beta MESH: Photoreceptor Cells MESH: Reverse Transcriptase Polymerase Chain Reaction MESH : Macrophages 0303 health sciences MESH : Rats [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Reverse Transcriptase Polymerase Chain Reaction Retinal Degeneration MESH : Reverse Transcriptase Polymerase Chain Reaction MESH: Enzyme-Linked Immunosorbent Assay Regular Article Anatomy Receptor antagonist MESH : Enzyme-Linked Immunosorbent Assay Endothelial stem cell Vascular endothelial growth factor MESH : Retinal Degeneration MESH : Nerve Degeneration Cytokine Choroidal neovascularization [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs MESH : Nerve Regeneration [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] medicine.symptom medicine.medical_specialty MESH: Rats medicine.drug_class MESH: Retinal Degeneration Enzyme-Linked Immunosorbent Assay MESH : Mice Inbred C57BL Biology MESH : Rats Wistar MESH : Photoreceptor Cells MESH : Interleukin-1beta Pathology and Forensic Medicine 03 medical and health sciences MESH: Mice Inbred C57BL Internal medicine MESH : Mice medicine [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Animals Photoreceptor Cells [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Rats Wistar [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs MESH: Mice 030304 developmental biology MESH : Choroidal Neovascularization Macrophages MESH: Choroidal Neovascularization MESH: Macrophages MESH: Rats Wistar Macular degeneration medicine.disease MESH : Disease Models Animal Choroidal Neovascularization eye diseases Nerve Regeneration Rats Mice Inbred C57BL Disease Models Animal Endocrinology chemistry [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Nerve Degeneration sense organs MESH: Disease Models Animal 030217 neurology & neurosurgery |
Zdroj: | American Journal of Pathology American Journal of Pathology, American Society for Investigative Pathology, 2011, 178 (5), pp.2416-23. ⟨10.1016/j.ajpath.2011.01.013⟩ American Journal of Pathology, American Society for Investigative Pathology, 2011, 178 (5), pp.2416-23. 〈10.1016/j.ajpath.2011.01.013〉 American Journal of Pathology, 2011, 178 (5), pp.2416-23. ⟨10.1016/j.ajpath.2011.01.013⟩ |
ISSN: | 0002-9440 1525-2191 |
Popis: | International audience; 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. |
Databáze: | OpenAIRE |
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