Glucocorticoid Receptor Transactivation Is Required for Glucocorticoid-Induced Ocular Hypertension and Glaucoma

摘要: Purpose Glucocorticoid (GC)-induced ocular hypertension (GC-OHT) is a serious side effect of prolonged GC therapy that can lead to glaucoma and permanent vision loss. GCs cause plethora changes in the trabecular meshwork (TM), an tissue regulates intraocular pressure (IOP). act through glucocorticoid receptor (GR), GR transcription both transactivation transrepression. Many anti-inflammatory properties are mediated by transrepression, while largely accounts for metabolic effects therapy. There no evidence showing which two mechanisms plays role GC-OHT. Methods GRdim transgenic mice (which have active transrepression impaired transactivation) wild-type (WT) C57BL/6J received weekly periocular dexamethasone acetate (DEX-Ac) injections. IOP, outflow facilities, biochemical TM were determined. Results did not develop GC-OHT after continued DEX treatment, WT had significantly increased IOP decreased facilities. Both eyes DEX-treated cultured cells isolated from reduced or change expression fibronectin, myocilin, collagen type I, α-smooth muscle actin (α-SMA). mouse (MTM) also significant reduction DEX-induced cytoskeletal changes, was clearly seen MTM cells. Conclusions We provide first regulating GC-mediated gene development This discovery suggests novel therapeutic approach treating inflammation without causing glaucoma.