Cannabinoid 2 receptor is a novel anti-inflammatory target in experimental proliferative vitreoretinopathy

Autor: Anuja Siwakoti, Christian Lehmann, Joanna Borowska-Fielding, Richard F. Porter, Brent Johnston, Melanie E. M. Kelly, Anna-Maria Szczesniak, James T. Toguri, Simon Gebremeskel
Rok vydání: 2017
Předmět:
Lipopolysaccharides
Male
0301 basic medicine
Pathology
medicine.medical_specialty
Proliferative vitreoretinopathy
Indoles
medicine.medical_treatment
Inflammation
Biology
Retina
Proinflammatory cytokine
Receptor
Cannabinoid
CB2
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Fibrosis
Cannabinoid Receptor Modulators
Endopeptidases
Dispase
Leukocytes
medicine
Animals
Mice
Knockout
Pharmacology
Dose-Response Relationship
Drug
Microglia
Cannabinoids
Macrophages
Anti-Inflammatory Agents
Non-Steroidal
Vitreoretinopathy
Proliferative
Endothelial Cells
medicine.disease
eye diseases
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
sense organs
Cannabinoid
medicine.symptom
030217 neurology & neurosurgery
Intravital microscopy
Zdroj: Neuropharmacology. 113:627-638
ISSN: 0028-3908
DOI: 10.1016/j.neuropharm.2016.08.030
Popis: Proliferative vitreoretinopathy (PVR) can develop after ocular trauma or inflammation and is a common complication of surgery to correct retinal detachment. Currently, there are no pharmacological treatments for PVR. Cannabinoids acting at cannabinoid 2 receptor (CB2R) can decrease inflammation and fibrosis. The objective of this study was to examine the anti-inflammatory actions of CB2R as a candidate novel therapeutic target in experimental PVR. PVR was induced by intravitreal injection of dispase in wild-type (WT) and CB2R genetic knockout (CB2R −/− ) mice. Ocular pathology was studied at 24 h or one week after dispase injection. CB2R modulation was examined in WT mice, using the CB2R agonist, HU308, and the CB2R antagonist, AM630. Histopathological scoring and quantification of microglia was used to evaluate tissue pathology. Quantitative PCR and multiplex assays were used to assess changes in proinflammatory cytokines. Intravital microscopy (IVM) was used to visualize and quantify leukocyte-endothelial adhesion to the iridial microcirculation. Activation of CB2R with HU308 in WT mice with PVR decreased mean histopathological scores, the number of microglia, and leukocyte adhesion compared to vehicle-treated animals. Conversely, an increase in histopathological scores and activated microglia was observed in PVR animals after treatment with AM630. CB2R −/− mice with PVR exhibited exacerbated ocular histopathology, increased microglia numbers, and elevated protein levels of cytokines as compared to WT mice. In conclusion, our results indicate that intervention at early stage PVR with CB2R agonists reduces ocular inflammation and disease severity. CB2R may represent a therapeutic target to prevent PVR progression and vision loss. This article is part of the Special Issue entitled ‘Lipid Sensing G Protein-Coupled Receptors in the CNS’.
Databáze: OpenAIRE
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