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

Anna Maria Szczesniak, Richard F. Porter, James T. Toguri, Joanna Borowska-Fielding, Simon Gebremeskel, Anuja Siwakoti, Brent Johnston, Christian Lehmann, Melanie E.M. Kelly

Producción científica: Contribución a una revistaArtículo de revisiónrevisión exhaustiva

31 Citas (Scopus)

Resumen

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’.

Idioma originalEnglish
Páginas (desde-hasta)627-638
Número de páginas12
PublicaciónNeuropharmacology
Volumen113
DOI
EstadoPublished - feb. 1 2017

Nota bibliográfica

Funding Information:
Supported by an operating grant to MEMK from the Canadian Institutes of Health Research (MOP-97768). Richard Porter was funded by a scholarship from the Dalhousie University Department of Ophthalmology and Visual Science: Dr. R. Evatt and Rita Mathers Graduate Scholarship.

Publisher Copyright:
© 2016

ASJC Scopus Subject Areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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