Anti-vascular endothelial growth factor acts on retinal microglia/macrophage activation in a rat model of ocular inflammation
| Autor: | Couturier A, Bousquet E, Zhao M, Mc, Naud, christophe klein, Jonet L, Tadayoni R, de Kozak Y, Behar-Cohen F |
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| Přispěvatelé: | Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'ophtalmologie [Hôtel-Dieu - Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Hopital Lariboisière, Service Ophtalmologie, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Eye Hospital, Department of Ophthalmology, Jules-Gonin, Eye Hospital', Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu, Hôpital Lariboisière, HAL UPMC, Gestionnaire |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
Vascular Endothelial Growth Factor A Calcium-Binding Proteins Microfilament Proteins Anti-Inflammatory Agents Nitric Oxide Synthase Type II Cell Count Macrophage Activation Antibodies Neutralizing Retina eye diseases Rats Uveitis Disease Models Animal Receptors Vascular Endothelial Growth Factor [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs Neutralization Tests [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs Animals Humans Microglia sense organs [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs Research Article |
| Zdroj: | Molecular Vision Molecular Vision, Molecular Vision, 2014, 20, pp.908-920 Europe PubMed Central Molecular Vision, 2014, 20, pp.908-920 Molecular Vision, vol. 20, pp. 908-920 |
| ISSN: | 1090-0535 |
| Popis: | International audience; PurposeTo evaluate whether anti-vascular endothelial growth factor (VEGF) neutralizing antibodies injected in the vitreous of rat eyes influence retinal microglia and macrophage activation. To dissociate the effect of anti-VEGF on microglia and macrophages subsequent to its antiangiogenic effect, we chose a model of acute intraocular inflammation.MethodsLewis rats were challenged with systemic lipopolysaccharide (LPS) injection and concomitantly received 5 µl of rat anti-VEGF-neutralizing antibody (1.5 mg/ml) in the vitreous. Rat immunoglobulin G (IgG) isotype was used as the control. The effect of anti-VEGF was evaluated at 24 and 48 h clinically (uveitis scores), biologically (cytokine multiplex analysis in ocular media), and histologically (inflammatory cell counts on eye sections). Microglia and macrophages were immunodetected with ionized calcium-binding adaptor molecule 1 (IBA1) staining and counted based on their differential shapes (round amoeboid or ramified dendritiform) on sections and flatmounted retinas using confocal imaging and automatic quantification. Activation of microglia was also evaluated with inducible nitric oxide synthase (iNOS) and IBA1 coimmunostaining. Coimmunolocalization of VEGF receptor 1 and 2 (VEGF-R1 and R2) with IBA1 was performed on eye sections with or without anti-VEGF treatment.ResultsNeutralizing rat anti-VEGF antibodies significantly decreased ocular VEGF levels but did not decrease the endotoxin-induced uveitis (EIU) clinical score or the number of infiltrating cells and cytokines in ocular media (interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α, and monocyte chemoattractant protein [MCP]-1). Eyes treated with anti-VEGF showed a significantly decreased number of activated microglia and macrophages in the retina and the choroid and decreased iNOS-positive microglia. IBA1-positive cells expressed VEGF-R1 and R2 in the inflamed retina.ConclusionsMicroglia and macrophages expressed VEGF receptors, and intravitreous anti-VEGF influenced the microglia and macrophage activation state. Taking into account that anti-VEGF drugs are repeatedly injected in the vitreous of patients with retinal diseases, part of their effects could result from unsuspected modulation of the microglia activation state. This should be further studied in other ocular pathogenic conditions and human pathology. |
| Databáze: | OpenAIRE |
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