Rod Photoreceptors Express GPR55 in the Adult Vervet Monkey Retina

Joseph Bouskila,Maurice Ptito,Christian Casanova,Jean-François Bouchard,Pasha Javadi,Steven Barnes

doi:10.1371/journal.pone.0081080

Joseph Bouskila, Maurice Ptito + Show 4 more

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https://doi.org/10.1371/journal.pone.0081080

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Journal: PloS one	Publication Date: Nov 14, 2013
Citations: 28	License type: CC BY 4.0

Affiliation: Université de Montréal, University of Copenhagen

Abstract

Cannabinoids exert their actions mainly through two receptors, the cannabinoid CB1 receptor (CB1R) and cannabinoid CB2 receptor (CB2R). In recent years, the G-protein coupled receptor 55 (GPR55) was suggested as a cannabinoid receptor based on its activation by anandamide and tetrahydrocannabinol. Yet, its formal classification is still a matter of debate. CB1R and CB2R expression patterns are well described for rodent and monkey retinas. In the monkey retina, CB1R has been localized in its neural (cone photoreceptor, horizontal, bipolar, amacrine and ganglion cells) and CB2R in glial components (Müller cells). The aim of this study was to determine the expression pattern of GPR55 in the monkey retina by using confocal microscopy. Our results show that GPR55 is strictly localized in the photoreceptor layer of the extrafoveal portion of the retina. Co-immunolabeling of GPR55 with rhodopsin, the photosensitive pigment in rods, revealed a clear overlap of expression throughout the rod structure with most prominent staining in the inner segments. Additionally, double-label of GPR55 with calbindin, a specific marker for cone photoreceptors in the primate retina, allowed us to exclude expression of GPR55 in cones. The labeling of GPR55 in rods was further assessed with a 3D visualization in the XZ and YZ planes thus confirming its exclusive expression in rods. These results provide data on the distribution of GPR55 in the monkey retina, different than CB1R and CB2R. The presence of GPR55 in rods suggests a function of this receptor in scotopic vision that needs to be demonstrated.

Highlights

The cannabis sativa plant contains a group of biologically active substances, termed cannabinoids (CBs), which influence many biological functions [1,2], including vision [3]
The present study investigates the presence of G-protein-coupled receptor 55 (GPR55) in the monkey retina, compares the spatial expression of GPR55 to that of CB1 receptor (CB1R) and CB2 receptor (CB2R), and proposes a putative role for GPR55 in retinal functions
Careful examination of photoreceptors stained with Sytox green, a nuclear stain, and GPR55 indicates an absence of GPR55 expression in the nuclei of rods (Figure 1E–F, arrows)

Summary

Introduction

The cannabis sativa (marijuana) plant contains a group of biologically active substances, termed cannabinoids (CBs), which influence many biological functions [1,2], including vision [3]. The CBs activate mainly two 7-transmembrane G protein-coupled receptors, the cannabinoid CB1 receptor (CB1R) that mediates most of the psychoactive effects of marijuana and the cannabinoid CB2 receptor (CB2R) that mediate the immunological effects. Following the identification and cloning of a novel human G-protein-coupled receptor 55 (GPR55), several cannabinoid ligands were shown to bind to it, suggesting that it could be a novel cannabinoid receptor [5]. Lysophosphatidylinositol (LPI), an endogenous lipid mediator, has been described as the first ligand that potently and efficaciously activates GPR55 [6,8,10,11]. GPR55 has been shown to associate with lipid rafts having an impact on the biological activity of this receptor [16]

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