{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:13:48Z","timestamp":1786115628745,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["NSTC 113-2320-B-040-011-MY3"],"award-info":[{"award-number":["NSTC 113-2320-B-040-011-MY3"]}]},{"DOI":"10.13039\/501100006578","name":"Chi-Mei Medical Center Liouying Research","doi-asserted-by":"publisher","award":["CLFHR10704"],"award-info":[{"award-number":["CLFHR10704"]}],"id":[{"id":"10.13039\/501100006578","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Adverse effects associated with prolonged corticosteroid therapy are strongly associated with increased intraocular pressure (IOP), which may progress to iatrogenic glaucoma and irreversible blindness if left untreated. Developing reliable animal models is essential for investigating corticosteroid-induced ocular hypertension and evaluating potential therapeutic strategies. In this study, we established a simple and non-invasive rat model of corticosteroid-induced ocular hypertension using topical application of Rinderon-A ointment. Longitudinal IOP measurements were performed weekly using a Tono-Pen in conscious rats throughout the 11-week experimental period. Rinderon-A treatment resulted in sustained bilateral IOP elevation, with an initial increase observed at week 1 (28.4 \u00b1 1.5 mmHg) and a maximal mean IOP of 31.2 \u00b1 0.7 mmHg at week 10. Rinderon-A-treated eyes exhibited a sustained ocular hypertensive response throughout the experimental period. Collectively, this model provides a reproducible platform for studying corticosteroid-associated ocular hypertension and may facilitate future investigations of therapeutic interventions.<\/jats:p>","DOI":"10.3390\/biology15151289","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:32:43Z","timestamp":1785846763000},"page":"1289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-Term Corticosteroid-Induced Ocular Hypertension Model Produced by Topical Rinderon-A Ointment Application"],"prefix":"10.3390","volume":"15","author":[{"given":"Hsin-Lin","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-4409","authenticated-orcid":false,"given":"Yung-Chang","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Chi-Mei Hospital Liou-Ying, Tainan 73657, Taiwan"},{"name":"Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan 73658, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9019-2178","authenticated-orcid":false,"given":"Jiann-Jou","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.survophthal.2012.08.003","article-title":"Intraocular pressure monitoring post intravitreal steroids: A systematic review","volume":"58","author":"Kiddee","year":"2013","journal-title":"Surv. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/0002-9394(89)90221-3","article-title":"Intraocular pressure and glaucoma","volume":"107","author":"Sommer","year":"1989","journal-title":"Am. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.survophthal.2020.01.002","article-title":"Steroid-induced glaucoma: Epidemiology, pathophysiology, and clinical management","volume":"65","author":"Roberti","year":"2020","journal-title":"Surv. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.yexcr.2017.08.012","article-title":"A novel RIPK1 inhibitor that prevents retinal degeneration in a rat glaucoma model","volume":"359","author":"Do","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1007\/s12325-016-0315-8","article-title":"Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure","volume":"33","author":"Sheppard","year":"2016","journal-title":"Adv. Ther."},{"key":"ref_7","first-page":"1274","article-title":"Intraocular pressure response to topical corticosteroids","volume":"24","author":"Armaly","year":"1965","journal-title":"Fed. Proc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1001\/archopht.1989.01070020286040","article-title":"Structural proteins of the neonatal and adult lamina cribrosa","volume":"107","author":"Morrison","year":"1989","journal-title":"Arch. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.exer.2010.08.005","article-title":"Pathophysiology of human glaucomatous optic nerve damage: Insights from rodent models of glaucoma","volume":"93","author":"Morrison","year":"2011","journal-title":"Exp. Eye Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1167\/iovs.04-0988","article-title":"Overexpression and properties of wild-type and Tyr437His mutated myocilin in the eyes of transgenic mice","volume":"46","author":"Zillig","year":"2005","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9019","DOI":"10.1128\/MCB.24.20.9019-9025.2004","article-title":"Genetically increasing Myoc expression supports a necessary pathologic role of abnormal proteins in glaucoma","volume":"24","author":"Gould","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/sj.eye.6701895","article-title":"Corticosteroid-induced glaucoma: A review of the literature","volume":"20","author":"Kersey","year":"2006","journal-title":"Eye"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1167\/iovs.18-26383","article-title":"Glucocorticoid Receptor Transactivation Is Required for Glucocorticoid-Induced Ocular Hypertension and Glaucoma","volume":"60","author":"Patel","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Faralli, J.A., Dimeo, K.D., Trane, R.M., and Peters, D. (2018). Absence of a secondary glucocorticoid response in C57BL\/6J mice treated with topical dexamethasone. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192665"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.exer.2015.06.002","article-title":"Animal models of glucocorticoid-induced glaucoma","volume":"141","author":"Overby","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_16","first-page":"50440","article-title":"A laser-induced mouse model of chronic ocular hypertension to characterize visual defects","volume":"78","author":"Feng","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/exer.1996.0184","article-title":"A rat model of chronic pressure-induced optic nerve damage","volume":"64","author":"Morrison","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1080\/10717544.2021.1998245","article-title":"Long-term corticosteroid-induced chronic glaucoma model produced by intracameral injection of dexamethasone-loaded PLGA microspheres","volume":"28","author":"Rodrigo","year":"2021","journal-title":"Drug Deliv."},{"key":"ref_19","first-page":"52400","article-title":"Experimental glaucoma induced by ocular injection of magnetic microspheres","volume":"96","author":"Bunker","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.ajpath.2025.11.009","article-title":"Mechanistic Insights into Glucocorticoid-Induced Ocular Hypertension Using Differences in Mouse Strain Responsiveness","volume":"196","author":"Patel","year":"2026","journal-title":"Am. J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108264","DOI":"10.1016\/j.jdiacomp.2022.108264","article-title":"Association of depression and parasympathetic activation with glycemic control in type 2 diabetes mellitus","volume":"36","author":"Lin","year":"2022","journal-title":"J. Diabetes Complicat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.1007\/s00210-024-03570-1","article-title":"Effect of ophthalmic preparation of methyldopa on induced ocular hypertension in rabbits","volume":"398","author":"Gatea","year":"2025","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"605489","DOI":"10.2147\/DDDT.S605489","article-title":"Effect of Rho Kinase Inhibitor RKI-1447 on Dexamethasone-Induced Ocular Hypertension and Its Molecular Mechanisms in Sprague-Dawley Rats","volume":"20","author":"Wu","year":"2026","journal-title":"Drug Des. Devel Ther."},{"key":"ref_24","first-page":"3415","article-title":"Effect of general anesthetics on IOP in rats with experimental aqueous outflow obstruction","volume":"41","author":"Jia","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/APO.0000000000000118","article-title":"Fundamentals and Advances in Tonometry","volume":"4","author":"Nuyen","year":"2015","journal-title":"Asia-Pac. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"281214","DOI":"10.1155\/2015\/281214","article-title":"Experimentally Induced Mammalian Models of Glaucoma","volume":"2015","author":"Ishikawa","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.exer.2014.06.013","article-title":"28-day intraocular pressure reduction with a single dose of brimonidine tartrate-loaded microspheres","volume":"125","author":"Fedorchak","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sharif, N.A., Millar, J.C., Zode, G., and Ota, T. (2024). Steroid-Induced Ocular Hypertension in Mice Is Differentially Reduced by Selective EP2, EP3, EP4, and IP Prostanoid Receptor Agonists. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063328"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ajo.2019.02.001","article-title":"The Genetic Influence on Corticosteroid-Induced Ocular Hypertension: A Field Positioned for Discovery","volume":"202","author":"Chan","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/S0140-6736(97)03392-8","article-title":"Risk of ocular hypertension or open-angle glaucoma in elderly patients on oral glucocorticoids","volume":"350","author":"Garbe","year":"1997","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1089\/jop.1987.3.185","article-title":"Steroid-induced ocular hypertension in the rabbit: A model using subconjunctival injections","volume":"3","author":"Hester","year":"1987","journal-title":"J. Ocul. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1016\/j.ophtha.2011.02.042","article-title":"Intraocular pressure outcome of patients with fluocinolone acetonide intravitreal implant for noninfectious uveitis","volume":"118","author":"Bollinger","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10147-003-0366-0","article-title":"Management of intraocular retinoblastoma and ocular prognosis","volume":"9","author":"Suzuki","year":"2004","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1089\/10430349950018887","article-title":"Suicide gene therapy for treatment of retinoblastoma in a murine model","volume":"10","author":"Hurwitz","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1172\/JCI69774","article-title":"Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma","volume":"124","author":"Zode","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_36","first-page":"58287","article-title":"A Model of Glaucoma Induced by Circumlimbal Suture in Rats and Mice","volume":"140","author":"He","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/S0022-3565(25)28751-1","article-title":"Effects of corticosteroids on ocular dynamics in rabbits","volume":"175","author":"Lorenzetti","year":"1970","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejphar.2014.11.029","article-title":"Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs","volume":"749","author":"Razali","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1159\/000109989","article-title":"Proteomic analysis of the trabecular meshwork of rats in a steroid-induced ocular hypertension model: Downregulation of type I collagen C-propeptides","volume":"39","author":"Shinzato","year":"2007","journal-title":"Ophthalmic Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s10384-007-0507-5","article-title":"Proteomic analysis of rat retina in a steroid-induced ocular hypertension model: Potential vulnerability to oxidative stress","volume":"52","author":"Miyara","year":"2008","journal-title":"Jpn. J. Ophthalmol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/15\/1289\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:30:36Z","timestamp":1785990636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/15\/1289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":40,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["biology15151289"],"URL":"https:\/\/doi.org\/10.3390\/biology15151289","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]}}}