Glucocorticoid receptor GRbeta regulates glucocorticoid-induced ocular hypertension in mice

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dc.creatorPatel, Gaurang C.
dc.creatorLiu, Yang
dc.creatorMillar, J. Cameron
dc.creatorClark, Abbot F.
dc.creator.orcid0000-0003-3594-6560 (Clark, Abbot F.)
dc.date.accessioned2022-09-13T16:34:17Z
dc.date.available2022-09-13T16:34:17Z
dc.date.issued2018-01-16
dc.description.abstractProlonged 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.
dc.description.sponsorshipThe study was supported by National Eye Institute (NEI) grant R01EY016242 to Abbot F. Clark.
dc.identifier.citationPatel, 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/s41598-018-19262-9
dc.identifier.issn2045-2322
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31726
dc.identifier.volume8
dc.publisherSpringer Nature
dc.relation.urihttps://doi.org/10.1038/s41598-018-19262-9
dc.rights.holder© The Author(s) 2018
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientific Reports
dc.subject.meshAnimals
dc.subject.meshCollagen Type I / metabolism
dc.subject.meshCytoskeletal Proteins / metabolism
dc.subject.meshDexamethasone / pharmacology
dc.subject.meshEye Proteins / metabolism
dc.subject.meshFemale
dc.subject.meshFibronectins / metabolism
dc.subject.meshGenetic Vectors / metabolism
dc.subject.meshGlucocorticoids / pharmacology
dc.subject.meshGlycoproteins / metabolism
dc.subject.meshIntraocular Pressure / drug effects
dc.subject.meshMale
dc.subject.meshMice
dc.subject.meshMice, Inbred C57BL
dc.subject.meshOcular Hypertension / etiology
dc.subject.meshOcular Hypertension / metabolism
dc.subject.meshOcular Hypertension / pathology
dc.subject.meshReceptors, Glucocorticoid / genetics
dc.subject.meshReceptors, Glucocorticoid / metabolism
dc.subject.meshTrabecular Meshwork / cytology
dc.subject.meshTrabecular Meshwork / drug effects
dc.subject.meshTrabecular Meshwork / metabolism
dc.titleGlucocorticoid receptor GRbeta regulates glucocorticoid-induced ocular hypertension in mice
dc.typeArticle
dc.type.materialtext

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