Abstract
Purpose: :
Cannabinoid receptors and their ligands constitute an endogenous signaling system that is found throughout the body, including the eye. This system can be activated by Δ9-tetrahydrocannabinol, a major drug of abuse. Modulation of ocular immune and inflammatory responses, and intraocular pressure gives cannabinoids therapeutic potential. CB1 cannabinoid receptors, the chief target of endogenous and exogenous cannabinoids, were first isolated in 1990. CB1 receptors are widely distributed in the human anterior eye but little is known of the architecture of ocular cannabinoid signaling. Several proteins have been identified that produce or break down endogenous cannabinoids (endocannabinoids or eCBs), or that modulate cannabinoid receptors. Learning the distribution of these proteins will be essential to identifying the circuitry of the endogenous ocular cannabinoid signaling system.
Methods: :
We have used immunohistochemistry to identify the localization of eight cannabinoid-related proteins in the murine anterior eye.
Results: :
Here we show that most of the cannabinoid-related proteins are expressed in the murine anterior eye. Of diacylglycerol lipase α and β (DGLα/β), implicated in the production of the eCB 2-arachidonoyl glycerol (2-AG) only the latter is expressed; of monoacylglycerol lipase (MGL) and α/β-hydrolase domain 6 (ABHD6), both implicated in the breakdown of 2-AG, are differentially expressed; of fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (NAAA) that have been shown to break down the eCB anandamide and related acyl amides, only the latter is present. We also detail the expression pattern of cannabinoid receptor interacting protein 1a (CRIP1a), a protein that may modulate CB1 function.
Conclusions: :
Our results indicate that cannabinoid signaling in the murine anterior eye is likely to take diverse forms extending beyond regulation of intraocular pressure.
Keywords: anatomy • immunohistochemistry • intraocular pressure