Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists
dc.creator | Sharif, Najam A. | |
dc.creator | Millar, J. Cameron | |
dc.creator | Zode, Gulab S. | |
dc.creator | Ota, Takashi | |
dc.date.accessioned | 2024-04-05T14:38:24Z | |
dc.date.available | 2024-04-05T14:38:24Z | |
dc.date.issued | 2024-03-28 | |
dc.description.abstract | 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 < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 microg/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%) > butaprost (65.2%) > rivenprost (58.4%) > 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. | |
dc.description.sponsorship | This research was funded by the National Eye Institute, EY026177, and Santen Inc. | |
dc.identifier.citation | Sharif, N. A., Millar, J. C., Zode, G., & Ota, T. (2024). Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists. International journal of molecular sciences, 25(6), 3328. https://doi.org/10.3390/ijms25063328 | |
dc.identifier.issn | 1422-0067 | |
dc.identifier.issue | 6 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12503/32534 | |
dc.identifier.volume | 25 | |
dc.publisher | MDPI | |
dc.relation.uri | https://doi.org/10.3390/ijms25063328 | |
dc.rights.holder | © 2024 by the authors. | |
dc.rights.license | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | International Journal of Molecular Sciences | |
dc.subject | Butaprost | |
dc.subject | EP2 receptor agonist | |
dc.subject | Iop | |
dc.subject | Pf-04217329 | |
dc.subject | ocular hypertension | |
dc.subject | steroid | |
dc.subject.mesh | Misoprostol / pharmacology | |
dc.subject.mesh | Misoprostol / therapeutic use | |
dc.subject.mesh | Ocular Hypertension / chemically induced | |
dc.subject.mesh | Ocular Hypertension / drug therapy | |
dc.subject.mesh | Acetamides | |
dc.subject.mesh | Acetates | |
dc.subject.mesh | Pyrazines | |
dc.subject.mesh | Sulfonamides | |
dc.title | Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists | |
dc.type | Article | |
dc.type.material | text |
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