Cannabinoid CB2R receptors are upregulated with corneal injury and regulate the course of corneal wound healing
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2019
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Experimental Eye Research
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Abstract
CB2R receptors have demonstrated beneficial effects in wound healing in several models. We
therefore investigated a potential role of CB2R receptors in corneal wound healing. We examined
the functional contribution of CB2R receptors to the course of wound closure in an in vivo murine
model. We additionally examined corneal expression of CB2R receptors in mouse and the
consequences of their activation on cellular signaling, migration and proliferation in cultured
bovine corneal epithelial cells (CECs). Using a novel mouse model, we provide evidence that
corneal injury increases CB2R receptor expression in cornea. The CB2R agonist JWH133 induces
chemorepulsion in cultured bovine CECs but does not alter CEC proliferation. The signaling
profile of CB2R activation is activating MAPK and increasing cAMP accumulation, the latter
perhaps due to Gs
-coupling. Lipidomic analysis in bovine cornea shows a rise in
acylethanolamines including the endocannabinoid anandamide 1 hour after injury. In vivo, CB2R
deletion and pharmacological block result in a delayed course of wound closure. In summary, we
find evidence that CB2R receptor promoter activity is increased by corneal injury and that these
receptors are required for the normal course of wound closure, possibly via chemorepulsion.
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Keywords
Cornea, Corneal wound healing, Lag phase, Cannabinoid, Endocannabinoid, CB2, Chemotaxis