Attribution 4.0 International (CC BY 4.0)2022-09-132022-09-132018-01-16Patel, G. C., Liu, Y., Millar, J. C., & Clark, A. F. (2018). Glucocorticoid receptor GRβ regulates glucocorticoid-induced ocular hypertension in mice. Scientific reports, 8(1), 862. https://doi.org/10.1038/s41598-018-19262-92045-2322https://hdl.handle.net/20.500.12503/31726Prolonged glucocorticoid (GC) therapy can cause GC-induced ocular hypertension (OHT), which if left untreated progresses to iatrogenic glaucoma and permanent vision loss. The alternatively spliced isoform of glucocorticoid receptor GRbeta acts as dominant negative regulator of GR activity, and it has been shown that overexpressing GRbeta in trabecular meshwork (TM) cells inhibits GC-induced glaucomatous damage in TM cells. The purpose of this study was to use viral vectors to selectively overexpress the GRbeta isoform in the TM of mouse eyes treated with GCs, to precisely dissect the role of GRbeta in regulating steroid responsiveness. We show that overexpression of GRbeta inhibits GC effects on MTM cells in vitro and GC-induced OHT in mouse eyes in vivo. Ad5 mediated GRbeta overexpression reduced the GC induction of fibronectin, collagen 1, and myocilin in TM of mouse eyes both in vitro and in vivo. GRbeta also reversed DEX-Ac induced IOP elevation, which correlated with increased conventional aqueous humor outflow facility. Thus, GRbeta overexpression reduces effects caused by GCs and makes cells more resistant to GC treatment. In conclusion, our current work provides the first evidence of the in vivo physiological role of GRbeta in regulating GC-OHT and GC-mediated gene expression in the TM.http://creativecommons.org/licenses/by/4.0/AnimalsCollagen Type I / metabolismCytoskeletal Proteins / metabolismDexamethasone / pharmacologyEye Proteins / metabolismFemaleFibronectins / metabolismGenetic Vectors / metabolismGlucocorticoids / pharmacologyGlycoproteins / metabolismIntraocular Pressure / drug effectsMaleMiceMice, Inbred C57BLOcular Hypertension / etiologyOcular Hypertension / metabolismOcular Hypertension / pathologyReceptors, Glucocorticoid / geneticsReceptors, Glucocorticoid / metabolismTrabecular Meshwork / cytologyTrabecular Meshwork / drug effectsTrabecular Meshwork / metabolismArticle© The Author(s) 201881