The Endocannabinoid System in the Vervet Monkey Retina

Abstract

The main active compound found in the marijuana plant, tetrahydrocannabinol, is responsible for its psychotropic effects but also for its numerous beneficial actions such as appetite stimulation, nausea reduction, analgesia, and muscle spasm suppressor. Although cannabis consumption leads to some visual disturbances, the exact role of the endocannabinoid system (ECS) in normal vision is still unknown. Many studies have looked into the localization of this complex system (receptors, ligands, and enzymes) throughout the various components of the visual system of different animal models in order to obtain clues about its role. In fact, the retina, optic nerve, dorsal lateral geniculate nucleus, and visual cortices all express parts of the ECS. Manipulating this system pharmacologically or genetically has also an impact on visual function. In this book chapter, we provide the current understanding of how the ECS is involved in the functioning of the visual system and special emphasis is put on data obtained in monkeys, representing the most relevant animal model for visual neuroscience research. The mechanisms that control endocannabinoid (eCB) release and activation of cannabinoid receptors are discussed. We also propose a model highlighting the mechanisms involved in the regulation of photopic and scotopic vision taking advantage of the spatial specificity of the eCB signaling system and its physiological activation conditions.

The Vertical and Horizontal Pathways in the Monkey Retina Are Modulated by Typical and Atypical Cannabinoid Receptors

“…Expression studies have shown that CB1R, CB2R, GPR55, and TRPV1 are present in the retina of multiple species [13,14,17,18,[21][22][23][24][25][26], but their differential expression has been found solely in the monkey retina [16,[27][28][29][30]. More precisely, our studies demonstrate that these receptors are distributed in the vertical and horizontal pathways of the vervet monkey retina.…”

“…Similarly, commercially available TRPV1 antibodies generate non-specific labeling in the retina of some species [33]. Using the non-human primate model and antibodies directed against human epitopes for cannabinoid receptors, in our experience, was found adequate [30,34]. In line with this, we compared the alignment of the human sequence for these 4 receptors (Figure 3).…”

The Inhibition of the Degrading Enzyme Fatty Acid Amide Hydrolase Alters the Activity of the Cone System in the Vervet Monkey Retina

“…Cannabinoid receptors are localized throughout the retina of several animal species [ 1 , 2 ], including primates [ 3 , 4 , 5 , 6 , 7 ]. In monkeys, the cannabinoid receptor type 1 (CB1R) is mainly expressed in the cones of the central retina [ 8 ], whereas the cannabinoid receptor type 2 (CB2R) is localized in the retinal glia (Müller cells) [ 9 ].…”

“…Full-field electroretinogram (ffERG) recordings represent a useful clinical tool to evaluate the integrity of the retina. The ffERG is a non-specific mass response made out of several retinal sources that are summed throughout the retina, and this method has been used for studying the eCB system in several animal species including mice and primates [ 1 , 3 , 4 , 14 , 15 , 16 , 17 ]. However, less is known about eCB signaling in cone responses using the photopic flicker ERG, especially in the 30 Hz flicker frequency that is known to activate mainly the cone system [ 18 ].…”

“…Manipulating the eCB system by blocking the activity of CB1R using intravitreal injections of the specific antagonist AM251 alters the global ffERG in the vervet monkey [ 14 ]. These results led to the suggestion that, in the primate model, CB1R acts as a mediator of central retinal function [ 4 ].…”