The Endocannabinoid System as a Therapeutic Target in Glaucoma

Figure 2

Cannabinoid-mediated alterations of the production and filtration of aqueous humor. Aqueous humor is formed by secretions from the ciliary body. Circulating aqueous humor (blue), flowing from the ciliary body in the posterior chamber to the anterior chamber, is filtered out of the eye through two different outflow pathways: the trabecular meshwork pathway (green) and the uveoscleral pathway (purple). The trabecular meshwork pathway involves the flow of aqueous humor through the trabecular meshwork to Schlemm’s canal, where it will exit through the episcleral veins. The uveoscleral pathway involves the flow of aqueous humor from the iridocorneal angle to the posterior chamber through the ciliary body, and out through the supraciliary and suprachoroidal spaces. CB₁, the major contributor to the IOP lowering effects of Δ⁹-THC and WIN 55,212-2, has been localized to the ciliary body, trabecular meshwork, and Schlemm’s canal [11, 13–15, 17]. The IOP lowering effects of NAGly and Abn-CBD, and possibly CBG-DMH, are due to the activation of GPR18, which has been localized to the ciliary epithelium and iris [26, 58]. Additional pharmacological evidence has suggested that CB₂ and GPR55 are localized within the trabecular meshwork [23, 28]; the contribution of these receptors to changes in IOP is unknown. COX-2 derived prostaglandins and prostamides are purported to exert actions through the uveoscleral pathway; however, the exact mechanism(s) is unclear [36, 62, 63]. Figure adapted from Riordan-Eva [94]. Italics indicate potential receptor localization which is not yet confirmed.