{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:43:02Z","timestamp":1790196182652,"version":"4.1.0"},"reference-count":94,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY026177"],"award-info":[{"award-number":["EY026177"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Santen Inc.","award":["EY026177"],"award-info":[{"award-number":["EY026177"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p &lt; 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 \u00b5g\/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2\/EP3\/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) &gt; butaprost (65.2%) &gt; rivenprost (58.4%) &gt; NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.<\/jats:p>","DOI":"10.3390\/ijms25063328","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T09:32:30Z","timestamp":1710495150000},"page":"3328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists"],"prefix":"10.3390","volume":"25","author":[{"given":"Najam A.","family":"Sharif","sequence":"first","affiliation":[{"name":"Ophthalmology Innovation Center, Santen Inc., Emeryville, CA 94608, USA"},{"name":"Institute of Ophthalmology, University College London (UCL), London EC1V 9EL, UK"},{"name":"Department of Ophthalmology, Imperial College of Science and Technology, St. Mary\u2019s Campus, London W2 1PG, UK"},{"name":"Department of Ophthalmology, Eye-ACP Duke-National University of Singapore Medical School, Singapore 119228, Singapore"},{"name":"Singapore Eye Research Institute (SERI), Singapore 168751, Singapore"},{"name":"Department of Pharmacy Sciences, Creighton University, Omaha, NE 68178, USA"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA"},{"name":"Department of Pharmacology & Neuroscience, North Texas Eye Research Institute (NTERI), University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Cameron","family":"Millar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Neuroscience, North Texas Eye Research Institute (NTERI), University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulab","family":"Zode","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Center for Translational Vision Research, University of California, Irvine, CA 92617, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2366-2819","authenticated-orcid":false,"given":"Takashi","family":"Ota","sequence":"additional","affiliation":[{"name":"Ophthalmology Innovation Center, Santen Pharmaceutical Co., Ltd., Nara 630-0101, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"978","DOI":"10.2174\/1570159X15666170915142727","article-title":"Novel Therapeutics in Glaucoma Management","volume":"16","author":"Bucolo","year":"2018","journal-title":"Curr. 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