Interactive reportCannabinoid receptor CB1 mRNA is highly expressed in the rat ciliary body: implications for the antiglaucoma properties of marihuana1
Introduction
Cannabinoids are known to exert various actions of potential medical interest, and several studies exploring their therapeutic effects on the eye have been published 1, 2, 3, 4, 5, 6. They have failed, however, to provide a clear explanation of the cellular and molecular mechanisms involved. Controversy still exists about cannabinoid gene 7, 19and protein [4]expression in the eye, and whether or not the effects of cannabinoids on intraocular pressure are directly mediated by cannabinoid receptors or through other transmitter systems 5, 6.
The recent cloning and characterization of central cannabinoid (CB1) 8, 9and peripheral (CB2) [10]receptors allows the employment of sensitive techniques such as reverse transcription-polymerase chain reaction (RT-PCR) for the measurement and comparison of their mRNA levels. This method revealed the expression of CB1, not only in the central nervous system but also, to a lesser extent, in several peripheral tissues such as the heart, lung, spleen and tonsils [7]. Conversely, CB2 transcripts, which are not expressed in the brain, were found to be abundant only in the immune tissue [7]. In humans, CB1 and CB2 mRNA are undetectable in the retina [7], while their expression in any of the eye's other structures was not explored.
The present study was undertaken in order to determine whether, and where, cannabinoid receptor mRNAs are expressed in the rat eye. For this purpose we used a RT-PCR method previously employed to measure and compare cannabinoid receptor mRNA levels in human tissues [7].
Section snippets
Animal experiments
Twenty Long–Evans rats were purchased from Charles River (Como, Italy). Animals were housed three or four per cage and given free access to food and water under controlled conditions of temperature (25°C) and humidity (65%), with a 12 h light/12 h darkness cycle. In order to minimize pain and discomfort for the animals, all the experiments were carried out in accordance with the European Community's Council Directive of 24 November 1986 (86/609/EEC).
The rats were sacrificed by decapitation. The
Eye preparation
In a preliminary series of experiments the rat's eye was studied in toto, after enucleation and after the removal of the vitreous and of the optic nerve from the optic pole. Since RT-PCR experiments demonstrated positive expression of the CB1, but not CB2, receptors, the anatomical regions of the rat's eye were further dissected, under a 100× stereomicroscope. The sclera, cornea, lens, ciliary body with iris, vitreous, terminal part of the optic nerve, retina and choroid were separated (Fig. 1)
Discussion
Some clinical 1, 2and preclinical [3]data suggest that cannabinoids could represent a new class of antiglaucoma agents. Research interest in this application remains, in spite of the controversy about the efficacy of cannabinoids in clinical ophthalmology 2, 5, 6, because it may help in understanding the physiology of intraocular pressure control. In topical administration, when the lipid solubility of Delta-9-tetrahydrocannabinol (Δ9-THC) was overcome by the use of mineral oil as the vehicle
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2021, International ImmunopharmacologyCannabinoids and the eye
2021, Survey of OphthalmologyCitation Excerpt :GPR18 receptors have been reported to be present in the hypothalamus, brainstem, cerebellum, and striatum of the brain, as well as the lungs, thyroid, thymus, spleen, testes, ovary, and peripheral blood leukocytes.44,69 In the eye, CB1 receptors have been identified in the corneal epithelium and endothelium, iris, ciliary body, trabecular meshwork, Schlemm canal, choroid, as well as the ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, and outer segments of photoreceptor cells of the retina26,79,113,114,133; CB2 receptors are expressed in the corneal and retinal pigment epithelium.99,147 Murine models have shown that GPR18 receptors are present in the corneal and ciliary epithelium and the trabecular meshwork.20
Cannabinoid CB2R receptors are upregulated with corneal injury and regulate the course of corneal wound healing
2019, Experimental Eye ResearchCitation Excerpt :Our finding in bovine cornea that injury elevates nearly all N-acyl ethanolamines tested including the CB1/CB2 endogenous ligand anandamide implicates these lipids as chemotaxic messengers. Turning to CB2R, previous studies of mRNA expression in anterior eye (e.g. (Porcella et al., 1998; Porcella et al., 2000)) and our own experiments conducted in collaboration with Dr. Shu-Jung Hu, suggested that CB2R mRNA was not present under baseline conditions. However, using quantitative PCR and a recently developed CB2R reporter mouse we observed an upregulation of CB2R 3 h after injury.
Medical use of cannabis for glaucoma
2019, Canadian Journal of OphthalmologyUtilisation médicale du cannabis pour le glaucome
2019, Canadian Journal of Ophthalmology
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Published on the World Wide Web on 5 June 1998.