Cannabinoid CB2R receptors are upregulated with corneal injury and regulate the course of corneal wound healing. Exp Eye Res 2019 May;182:74-84
Date
03/25/2019Pubmed ID
30905716Pubmed Central ID
PMC6504573DOI
10.1016/j.exer.2019.03.011Scopus ID
2-s2.0-85063275776 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
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 h 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.
Author List
Murataeva N, Miller S, Dhopeshwarkar A, Leishman E, Daily L, Taylor X, Morton B, Lashmet M, Bradshaw H, Hillard CJ, Romero J, Straiker AAuthor
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCannabinoids
Cell Movement
Cell Proliferation
Cells, Cultured
Chemotaxis
Corneal Injuries
Disease Models, Animal
Epithelial Cells
Epithelium, Corneal
Mice
Receptors, Cannabinoid
Signal Transduction
Wound Healing
