Role of the alternatively spliced glucocorticoid receptor isoform GRβ in steroid responsiveness and glaucoma

Ankur Jain, Robert J. Wordinger, Thomas Yorio, Abbot Clark

Research output: Contribution to journalReview articleResearchpeer-review

12 Citations (Scopus)

Abstract

Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious side effect of GC therapy in susceptible individuals. This OHT is due to increased aqueous humor (AH) outflow resistance in the trabecular meshwork (TM) caused by GC-mediated changes in TM structure and function. GCs may also play a role in the development of primary open-angle glaucoma (POAG). Elevated cortisol levels in the AH or enhanced GC sensitivity may be one of the reasons for elevated intraocular pressure in POAG patients. The GC OHT responder population is at greater risk of developing POAG compared with non-responders. We recently have gained insight into the molecular mechanisms responsible for this differential GC responsiveness, which is attributed to differences in GC receptor isoform expression in the TM. This article summarizes current knowledge on alternative GC receptor splicing to generate GC receptor alpha (GRα) and GRβ and their roles in the regulation of GC responsiveness in normal and glaucoma TM.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalJournal of Ocular Pharmacology and Therapeutics
Volume30
Issue number2-3
DOIs
StatePublished - 1 Mar 2014

Fingerprint

Glucocorticoid Receptors
Glaucoma
Glucocorticoids
Protein Isoforms
Trabecular Meshwork
Steroids
Ocular Hypertension
Aqueous Humor
Intraocular Pressure
Hydrocortisone
Population
Primary Open Angle Glaucoma

Cite this

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abstract = "Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious side effect of GC therapy in susceptible individuals. This OHT is due to increased aqueous humor (AH) outflow resistance in the trabecular meshwork (TM) caused by GC-mediated changes in TM structure and function. GCs may also play a role in the development of primary open-angle glaucoma (POAG). Elevated cortisol levels in the AH or enhanced GC sensitivity may be one of the reasons for elevated intraocular pressure in POAG patients. The GC OHT responder population is at greater risk of developing POAG compared with non-responders. We recently have gained insight into the molecular mechanisms responsible for this differential GC responsiveness, which is attributed to differences in GC receptor isoform expression in the TM. This article summarizes current knowledge on alternative GC receptor splicing to generate GC receptor alpha (GRα) and GRβ and their roles in the regulation of GC responsiveness in normal and glaucoma TM.",
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Role of the alternatively spliced glucocorticoid receptor isoform GRβ in steroid responsiveness and glaucoma. / Jain, Ankur; Wordinger, Robert J.; Yorio, Thomas; Clark, Abbot.

In: Journal of Ocular Pharmacology and Therapeutics, Vol. 30, No. 2-3, 01.03.2014, p. 121-127.

Research output: Contribution to journalReview articleResearchpeer-review

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AB - Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious side effect of GC therapy in susceptible individuals. This OHT is due to increased aqueous humor (AH) outflow resistance in the trabecular meshwork (TM) caused by GC-mediated changes in TM structure and function. GCs may also play a role in the development of primary open-angle glaucoma (POAG). Elevated cortisol levels in the AH or enhanced GC sensitivity may be one of the reasons for elevated intraocular pressure in POAG patients. The GC OHT responder population is at greater risk of developing POAG compared with non-responders. We recently have gained insight into the molecular mechanisms responsible for this differential GC responsiveness, which is attributed to differences in GC receptor isoform expression in the TM. This article summarizes current knowledge on alternative GC receptor splicing to generate GC receptor alpha (GRα) and GRβ and their roles in the regulation of GC responsiveness in normal and glaucoma TM.

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