The Pharmacology of Cannabinoids and Cannabimimetic Ligands in the Eye and their Effects on Intraocular Pressure
Cannabinoids produce ocular hypotension via activation of cannabinoid receptor type 1 (CB1). Adrenergic receptors (ARs) may contribute to this effect. Recently de-orphaned receptors, GPR55 and GPR18, are activated by some cannabinoids, but their role in IOP modulation is unknown. This research examined CB1-mediated IOP reduction by cannabinoids and tested whether ligands that activate GPR55 and GPR18 reduce IOP. Measurement of IOP was made using rebound tonometry in wild-type (WT) mice, and mice lacking βARs, GPR55, or cannabinoid receptors. CB1 or βAR knock-out, or βAR desensitization and catecholamine depletion in WT mice eliminated IOP reduction by cannabinoids. CB2 and GPR55 activation in WT mice failed to reduce IOP. Activation of GPR18 by selective and non-selective agonists reduced IOP and the GPR55/GPR18 antagonist, 0-1918, blocked this effect. These findings suggest that cannabinoids reduce IOP via a CB1-mediated reduction in catecholamine release and that GPR18 activation reduces IOP independent of CB1/CB.