Inhibition of dexamethasone-induced cytoskeletal changes in cultured human trabecular meshwork cells by tetrahydrocortisol.

摘要: Purpose. To determine the cellular mechanism of action intraocular pressure (IOP) lowering steroid tetrahydrocortisol (THF). Methods. Tetrahydrocortisol was evaluated for glucocorticoid antagonist activity using in vitro and vivo assays. Systemically administered THF its ability to inhibit dexamethasone-induced body weight loss systemic hypertension rats. In receptor antagonism tested supernatant fraction IM9 cells as source soluble 3 H-dexamethasone displacement binding addition, six different primary human trabecular meshwork (TM) cell lines were cultured 0 14 days absence or presence dexamethasone (10 -7 M) and/or -6 10 -8 M). The effects these steroids on TM cytoskeleton determined by epifluorescent microscopy transmission electron microscopy. Results. unable (DEX)-induced decrease mass rats displace H-DEX from receptor. However, inhibited DEX-induced formation cross-linked actin networks a progressive dose-dependent manner (IC 50 = 5.7 X Dexamethasone caused changes microtubules that reversed partially concomitant treatment with THF. alone appeared increase microfilament bundling cells. Conclusions. not at level classical did appear antagonize systemically mediated rat. microfilaments microtubules. These results may explain IOP because glucocorticoid-mediated have been proposed be involved generation ocular hypertension.