{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:46:29Z","timestamp":1786549589911,"version":"build-2736575974"},"reference-count":103,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:00:00Z","timestamp":1697241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["EY016242"],"award-info":[{"award-number":["EY016242"]}]},{"name":"NIH","award":["EY030967"],"award-info":[{"award-number":["EY030967"]}]},{"name":"research collaborators, as well as former graduate students and postdoctoral fellows from the Clark lab","award":["EY016242"],"award-info":[{"award-number":["EY016242"]}]},{"name":"research collaborators, as well as former graduate students and postdoctoral fellows from the Clark lab","award":["EY030967"],"award-info":[{"award-number":["EY030967"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The glucocorticoid receptor (GR), including both alternative spliced isoforms (GR\u03b1 and GR\u03b2), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases\/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e., GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have a lower expression of GR\u03b2, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. An increased expression of GR\u03b2 can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. The endogenous expression of GR\u03b2 in the TM may relate to differences in the development of GC-OHT in the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease-modifying therapies to better treat these two sight threatening forms of glaucoma. The purpose of this timely review is to highlight the pathological and clinical features of GC-OHT and GIG, mechanisms responsible for GC responsiveness, potential therapeutic options, as well as to compare the similar features of GIG with POAG.<\/jats:p>","DOI":"10.3390\/cells12202452","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T14:38:42Z","timestamp":1697294322000},"page":"2452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7704-4381","authenticated-orcid":false,"given":"Pinkal D.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Pharmacology & Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4956-841X","authenticated-orcid":false,"given":"Bindu","family":"Kodati","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3594-6560","authenticated-orcid":false,"given":"Abbot F.","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.ogla.2020.12.007","article-title":"Clinical and Economic Burden of Glaucoma by Disease Severity: A United States Claims-Based Analysis","volume":"4","author":"Shih","year":"2021","journal-title":"Ophthalmol. 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