Mifepristone blocks specific glucocorticoid receptor binding in rabbit iris-ciliary body

Mifepristone is a specific glucocorticoid receptor antagonist that has been shown to lower intraocular pressure modestly when applied topically to rabbit eyes. We evaluated the ability of mifepristone to block specific in vitro glucocorticoid receptor binding of the labeled agonist triamcinolone acetonide in cytosol isolated from rabbit iris-ciliary body tissue. A 500-fold molar excess of nonradioactive mifepristone completely blocked specific binding of triamcinolone acetonide to glucocorticoid receptors in the iris-ciliary body cytosol. Additionally, specific binding was blocked in a dose-dependent fashion over a range of 0.005-fold to 500-fold molar excess of mifepristone. Mifepristone's effect on intraocular pressure may be due to its ability to antagonize glucocorticoid receptor-mediated effects in ocular tissues.