{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T02:43:31Z","timestamp":1778035411807,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health Grants","doi-asserted-by":"publisher","award":["T32ES011564"],"award-info":[{"award-number":["T32ES011564"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health Grants","doi-asserted-by":"publisher","award":["R5385"],"award-info":[{"award-number":["R5385"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Louisville Research Infrastructure Fund","award":["T32ES011564"],"award-info":[{"award-number":["T32ES011564"]}]},{"name":"University of Louisville Research Infrastructure Fund","award":["R5385"],"award-info":[{"award-number":["R5385"]}]},{"name":"University of Louisville Integrated Program Biological Science Fellowship","award":["T32ES011564"],"award-info":[{"award-number":["T32ES011564"]}]},{"name":"University of Louisville Integrated Program Biological Science Fellowship","award":["R5385"],"award-info":[{"award-number":["R5385"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Intraocular pressure (IOP) is regulated primarily through aqueous humor production by ciliary body and drainage through uveoscleral and trabecular meshwork (TM) tissues. The goal of this study was to measure the effect of non-psychotropic cannabidiol (CBD) on aqueous humor outflow through TM and assess the effect of CBD on the TM cell signaling pathways that are important for regulating outflow. Perfused porcine eye anterior segment explants were used to investigate the effects of CBD on aqueous humor outflow. Cultured porcine TM cells were used to study the effects of CBD on TM cell contractility, myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation, and RhoA activation. In the anterior segment perfusion experiments, aqueous humor outflow was increased significantly within 1 h after adding 1 \u00b5M CBD and the effect was sustained over the 5 h of measurement. Treatment of TM cells with 1 \u00b5M CBD significantly decreased TM cell-mediated collagen contraction, inhibited phosphorylation of MLC and MYPT1, and reduced RhoA activation. Our data demonstrate, for the first time, that as a potential therapeutic agent for lowering intraocular pressure, CBD can enhance aqueous humor outflow and modify TM cell signaling.<\/jats:p>","DOI":"10.3390\/cells11193006","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T21:23:27Z","timestamp":1664313807000},"page":"3006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Effects of Cannabidiol on Aqueous Humor Outflow and Trabecular Meshwork Cell Signaling"],"prefix":"10.3390","volume":"11","author":[{"given":"Alyssa S.","family":"Aebersold","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao-Hui","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1097\/01.icu.0000156136.20570.eb","article-title":"Glaucoma medication and aqueous humor dynamics","volume":"16","author":"Crowston","year":"2005","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/S0140-6736(04)16257-0","article-title":"Primary open-angle glaucoma","volume":"363","author":"Weinreb","year":"2004","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The Pathophysiology and Treatment of Glaucoma: A review","volume":"311","author":"Weinreb","year":"2014","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1080\/14656566.2020.1795130","article-title":"Current and new pharmacotherapeutic approaches for glaucoma","volume":"21","author":"Shalaby","year":"2020","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_6","first-page":"111","article-title":"Novel Pharmacologic Candidates for Treatment of Primary Open-Angle Glaucoma","volume":"90","author":"Lu","year":"2017","journal-title":"Yale J. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"824","DOI":"10.2174\/156652410793937778","article-title":"Pharmacotherapies for Glaucoma","volume":"10","author":"Toris","year":"2010","journal-title":"Curr. Mol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1080\/14656566.2017.1408791","article-title":"New pharmacotherapy for the treatment of glaucoma","volume":"18","author":"Schehlein","year":"2017","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.tips.2009.07.006","article-title":"Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herb","volume":"30","author":"Izzo","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1590\/S1516-44462008000300015","article-title":"Cannabidiol: From an inactive cannabinoid to a drug with wide spectrum of action","volume":"30","author":"Zuardi","year":"2008","journal-title":"Rev. Bras. Psiquiatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1365-2125.2012.04298.x","article-title":"Cannabidiol as potential anticancer drug","volume":"75","author":"Massi","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1002\/ptr.4781","article-title":"Cannabidiol in Inflammatory Bowel Diseases: A Brief Overview","volume":"27","author":"Esposito","year":"2012","journal-title":"Phytotherapy Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1755-5949.2008.00065.x","article-title":"Cannabidiol: A Promising Drug for Neurodegenerative Disorders?","volume":"15","author":"Iuvone","year":"2009","journal-title":"CNS Neurosci. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1365-2125.2012.04341.x","article-title":"Cannabidiol for neurodegenerative disorders: Important new clinical applications for this phytocannabinoid?: Cannabidiol and Neurodegenerative Disorders","volume":"75","author":"Sagredo","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5131","DOI":"10.2174\/138161212802884681","article-title":"A Critical Review of the Antipsychotic Effects of Cannabidiol: 30 Years of a Translational Investigation","volume":"18","author":"Zuardi","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","unstructured":"(2022, August 15). FDA. Epidiolex: Highlights of prescribing information. 2018, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/210365lbl.pdf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1001\/jama.1971.03190100074024","article-title":"Marihuana smoking and intraocular pressure","volume":"217","author":"Hepler","year":"1971","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1136\/bjo.2003.032250","article-title":"Cannabinoids and glaucoma","volume":"88","author":"Tomida","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.33594\/000000371","article-title":"Cannabidiol Signaling in the Eye and Its Potential as an Ocular Therapeutic Agent","volume":"55","author":"Aebersold","year":"2021","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Passani, A., Posarelli, C., Sframeli, A.T., Perciballi, L., Pellegrini, M., Guidi, G., and Figus, M. (2020). Cannabinoids in Glaucoma Patients: The Never-Ending Story. J. Clin. Med., 9.","DOI":"10.3390\/jcm9123978"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.exer.2004.08.029","article-title":"Regulation of myosin light chain phosphorylation in the trabecular meshwork: Role in aqueous humour outflow facility","volume":"80","author":"Rao","year":"2005","journal-title":"Exp. Eye Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e60831","DOI":"10.7554\/eLife.60831","article-title":"Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis","volume":"10","author":"Li","year":"2021","journal-title":"eLife"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s40265-019-01130-z","article-title":"Rho-Associated Kinase Inhibitors: Evolving Strategies in Glaucoma Treatment","volume":"79","author":"Schehlein","year":"2019","journal-title":"Drugs"},{"key":"ref_24","first-page":"1029","article-title":"Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632","volume":"42","author":"Rao","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S1350-9462(99)00015-4","article-title":"The regulation of trabecular meshwork and ciliary muscle contractility","volume":"19","author":"Wiederholt","year":"2000","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/cm.20472","article-title":"Rho-kinase\/ROCK: A key regulator of the cytoskeleton and cell polarity","volume":"67","author":"Amano","year":"2010","journal-title":"Cytoskeleton"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0014-4835(02)00255-5","article-title":"The role of protein kinase C in modulation of aqueous humor outflow facility","volume":"76","author":"Khurana","year":"2002","journal-title":"Exp. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3109\/08820539909061466","article-title":"Advances in Glaucoma Diagnosis and Therapy for the Next Millennium: New Drugs for Trabecular and Uveoscleral Outflow","volume":"14","author":"Kaufman","year":"1999","journal-title":"Semin. Ophthalmol."},{"key":"ref_29","first-page":"74","article-title":"Acto-myosin drug effects and aqueous outflow function","volume":"40","author":"Epstein","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Vitale, R., Iannotti, F., and Amodeo, P. (2021). The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094876"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1167\/iovs.04-0651","article-title":"CB2 Cannabinoid Receptors in Trabecular Meshwork Cells Mediate JWH015-Induced Enhancement of Aqueous Humor Outflow Facility","volume":"46","author":"Zhong","year":"2005","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1167\/iovs.05-0729","article-title":"Noladin Ether Acts on Trabecular Meshwork Cannabinoid (CB1) Receptors to Enhance Aqueous Humor Outflow Facility","volume":"47","author":"Njie","year":"2006","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.exer.2008.05.003","article-title":"Aqueous humor outflow effects of 2-arachidonylglycerol","volume":"87","author":"Njie","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4528","DOI":"10.1167\/iovs.07-1537","article-title":"N-arachidonylethanolamide-Induced Increase in Aqueous Humor Outflow Facility","volume":"49","author":"Njie","year":"2008","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_35","first-page":"2649","article-title":"Effect of matrix metalloproteinases activity on outflow in perfused human organ culture","volume":"39","author":"Bradley","year":"1998","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","first-page":"1043","article-title":"Human trabecular cells. I. Establishment in tissue culture and growth characteristics","volume":"18","author":"Polansky","year":"1979","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S0014-4835(82)80074-2","article-title":"Human trabecular endothelium, corneal endothelium, keratocytes, and scleral fibroblasts in primary cell culture. A comparative study of growth characteristics, morphology, and phagocytic activity by light and scanning electron microscopy","volume":"35","author":"Tripathi","year":"1982","journal-title":"Exp. Eye Res."},{"key":"ref_38","first-page":"74","article-title":"Signaling mechanism of TGF-beta1-induced collagen contraction mediated by bovine trabecular meshwork cells","volume":"43","author":"Nakamura","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","first-page":"1348","article-title":"Molecular and cellular changes induced by the activation of CB2 cannabinoid receptors in trabecular meshwork cells","volume":"13","author":"He","year":"2007","journal-title":"Mol. Vis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/0306-3623(84)90202-7","article-title":"Ocular hypotension, ocular toxicity, and neurotoxicity in response to marihuana extract and cannabidiol","volume":"15","author":"Colasanti","year":"1984","journal-title":"Gen. Pharmacol. Vasc. Syst."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0014-4835(78)90092-1","article-title":"A comparison of topical cannabinoids on intraocular pressure","volume":"27","author":"Green","year":"1978","journal-title":"Exp. Eye Res."},{"key":"ref_42","unstructured":"Perez-reyes, M., Wagner, D., Wall, M.E., and Davis, K.H. (1976). Intravenous administration of cannabinoids and intraocular pressure. Pharmacology of Marihuana, Raven Press."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2165\/00063030-200721030-00004","article-title":"Rho GTPase\/Rho Kinase Inhibition as a Novel Target for the Treatment of Glaucoma","volume":"21","author":"Rao","year":"2007","journal-title":"BioDrugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1161\/01.RES.0000255894.25293.82","article-title":"Myosin Phosphatase Regulatory Pathways","volume":"100","author":"Lincoln","year":"2007","journal-title":"Circ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"102935","DOI":"10.1016\/j.drugpo.2020.102935","article-title":"Access to cannabidiol without a prescription: A cross-country comparison and analysis","volume":"85","author":"McGregor","year":"2020","journal-title":"Int. J. Drug Policy"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1089\/can.2016.0034","article-title":"An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies","volume":"2","author":"Iffland","year":"2017","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1038\/s41386-020-0667-2","article-title":"Adverse effects of cannabidiol: A systematic review and meta-analysis of randomized clinical trials","volume":"45","author":"Chesney","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5904","DOI":"10.1167\/iovs.18-24838","article-title":"\u03949-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure","volume":"59","author":"Miller","year":"2018","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"121627","DOI":"10.1016\/j.ijpharm.2022.121627","article-title":"The dose-dependent effect of a stabilized cannabidiol nanoemulsion on ocular surface inflammation and intraocular pressure","volume":"617","author":"Rebibo","year":"2022","journal-title":"Int. J. Pharm."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/19\/3006\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:40:04Z","timestamp":1760143204000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/19\/3006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,27]]},"references-count":49,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cells11193006"],"URL":"https:\/\/doi.org\/10.3390\/cells11193006","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,27]]}}}