ArticleInvestigative ophthalmology & visual science2016
Harnessing the Endocannabinoid 2-Arachidonoylglycerol to Lower Intraocular Pressure in a Murine Model.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Unveiling the role of CB2 receptor in beta-hydroxybutyrate mediated modulation of.Journal of physiology and biochemistry · 2026Article
- The Endocannabinoid System in Retinal Müller Glia: Lessons From Astrocyte Research.Neurochemical research · 2025Review
- Cannabinoids as Multitarget Drugs for the Treatment of Autoimmunity in Glaucoma.ACS pharmacology & translational science · 2025Review
- Cannabinoid CB1 receptors regulate salivation.Scientific reports · 2022Article
- Inhibition of triple negative breast cancer-associated inflammation, tumor growth and brain colonization by targeting monoacylglycerol lipase.Scientific reports · 2022Article
- A Proteomic View of Cellular and Molecular Effects of Cannabis.Biomolecules · 2021Review
- Endocannabinoid metabolism and transport as targets to regulate intraocular pressure.Experimental eye research · 2020Article
- THC Regulates Tearing via Cannabinoid CB1 Receptors.Investigative ophthalmology & visual science · 2020Article
- Synthesis and evaluation of potent and selective MGL inhibitors as a glaucoma treatment.Bioorganic & medicinal chemistry · 2019Article
- Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure.Investigative ophthalmology & visual science · 2018Article
- Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options.Neuronal signaling · 2018Review
- Controlled-Deactivation CB1 Receptor Ligands as a Novel Strategy to Lower Intraocular Pressure.Pharmaceuticals (Basel, Switzerland) · 2018Article
- Neuroprotection by (endo)Cannabinoids in Glaucoma and Retinal Neurodegenerative Diseases.Current neuropharmacology · 2018Review
- The In Vivo Effects of the CBJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2017Article
- A GPR119 Signaling System in the Murine Eye Regulates Intraocular Pressure in a Sex-Dependent Manner.Investigative ophthalmology & visual science · 2017Article
- Association between Plasma Metabolite Levels and Myopia: A 2-Sample Mendelian Randomization Study.Ophthalmology scienceArticle
- Role of Endocannabinoids in Glaucoma: A Review.Journal of current glaucoma practiceReview
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeCannabinoids, such as Δ9-THC, act through an endogenous signaling system in the vertebrate eye that reduces IOP via CB1 receptors. Endogenous cannabinoid (eCB) ligand, 2-arachidonoyl glycerol (2-AG), likewise activates CB1 and is metabolized by monoacylglycerol lipase (MAGL). We investigated ocular 2-AG and its regulation by MAGL and the therapeutic potential of harnessing eCBs to lower IOP.
methodsWe tested the effect of topical application of 2-AG and MAGL blockers in normotensive mice and examined changes in eCB-related lipid species in the eyes and spinal cord of MAGL knockout (MAGL-/-) mice using high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). We also examined the protein distribution of MAGL in the mouse anterior chamber.
results2-Arachidonoyl glycerol reliably lowered IOP in a CB1- and concentration-dependent manner. Monoacylglycerol lipase is expressed prominently in nonpigmented ciliary epithelium. The MAGL blocker KML29, but not JZL184, lowered IOP. The ability of CB1 to lower IOP is not desensitized in MAGL-/- mice. Ocular monoacylglycerols, including 2-AG, are elevated in MAGL-/- mice but, in contrast to the spinal cord, arachidonic acid and prostaglandins are not changed.
conclusionsOur data confirm a central role for MAGL in metabolism of ocular 2-AG and related lipid species, and that endogenous 2-AG can be harnessed to reduce IOP. The MAGL blocker KML29 has promise as a therapeutic agent, while JZL184 may have difficulty crossing the cornea. These data, combined with the relative specificity of MAGL for ocular monoacylglycerols and the lack of desensitization in MAGL-/- mice, suggest that the development of an optimized MAGL blocker offers therapeutic potential for treatment of elevated IOP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.