Project description:Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells. Gene expression changes of human trabecular meshwork cells, TM 86 and TM 93, due to treatment with dexamethasone (Dex), fluocinolone acetonide (FA), and triamcinolone acetonide (TA).
Project description:Background: the major risk factor for glaucoma is ocular hypertension, a disorder caused by reduced outflow of aqueous humor through the trabecular meshwork. In a previous pharmacogenomic screen for genes associated with ocular hypertension, we identified the novel G protein-coupled receptor, GPR158, and showed it protects against age-related ocular hypertension in mice. Here we show that the glucocorticoid, dexamethasone, increases the level of accumulated GPR158 protein in the trabecular meshwork of the human eye, ex vivo. Methods: we performed gene expression microarray profiling of TM-1 cells thar overexpress GPR158 Results: we show that the glucocorticoid, dexamethasone, increases the level of accumulated GPR158 protein in the trabecular meshwork of the human eye, ex vivo. Gene sets controlled by dexamethasone, TGFB1 and TP53 were identified, as well as genes asso-ciated with ossification. GPR158 over-expression in cells of the immortalized trabecular meshwork cell line TM-1 did not affect the fibrotic response to dexamethasone or cause ossification, and loss of GPR158 in knockout mice did not affect the development of glucocorticoid-induced ocular hypertension. However, GPR158 over-expression was cytoprotective. Discussion: Our findings suggest that GPR158 activated the cytoprotective branch of the unfolded protein response and bound the TP53-inducible protein PPP1R10, a regulatory subunit of PPI regulatory subunit of PPI. Our data support the idea that GPR158 protects the trabecular meshwork, and suggest possible mechanisms.
Project description:To clarify the effects of dexamethasone treatment for primary trabecular meshwork cell gene expression, which may relates to the pathophysiology of glucocorticoid-induced glaucoma Three lots (lot #2584, 3423 and 4973) of primary culture human trabecular meshwork (TM) cells were purchased from ScienCell Research Laboratories (Carlsbad, CA). The TM cells were treated with and without 100nM dexamethasone (DEX) for 14 days. Genomewide gene expression analysis was carried out using Agilent 8X60K array.
Project description:To clarify the effects of dexamethasone treatment for primary trabecular meshwork cell gene expression, which may relates to the pathophysiology of glucocorticoid-induced glaucoma
Project description:One of the undesirable side effects of glucocorticoid use is the potential development of elevated intraocular pressure and glaucoma. The precise mechanisms through which steroid use induces ocular hypertension are unclear. The purpose of this study was to identify gene expression changes induced by steroids in the human trabecular meshwork and the underlying sclerocorneal tissue.
Project description:One of the undesirable side effects of glucocorticoid use is the potential development of elevated intraocular pressure and glaucoma. The precise mechanisms through which steroid use induces ocular hypertension are unclear. The purpose of this study was to identify gene expression changes induced by steroids in the human trabecular meshwork and the underlying sclerocorneal tissue. The anterior segment of five pairs of adult human donor eyes were maintained in a profusion organ culture system.
