Interaction Between Progesterone and Mifepristone on Intraocular Pressure in Rabbits

Abstract

The interaction between a topically administered progesterone, medrysone, and a steroid antagonist, mifepristone, on rabbit intraocular pressure (IOP) has been determined. Medrysone alone increased IOP significantly above parallel controls over the first three weeks; this increase was not sustained. When medrysone and mifepristone were given simultaneously the IOP increased initially, but then fell after two weeks to control levels. When mifepristone was added 14 days after medrysone, the IOP was again reduced to, or below, control levels by mifepristone. The use of mifepristone alone reduced IOP relative to controls and the further addition of medrysone at 14 days had no effect on IOP. It appears that mifepristone is an effective antagonist against progesterone effects on IOP.

Effects of Mifepristone on Rabbit Intraocular Pressure in the Presence and Absence of Dexamethasone

“…= dexamethasone; RU486 = mifepristone. The more decisive results obtained with mifepristone [10] against progesterone stand in contradistinction to the present results. No obvious explanations exist for these dif ferences despite the use of drop application regimens, strain of rabbit and the use of a dexamethasone salt rather than an alcohol, that previously had resulted in an IOP in crease [14], The question of whether there is a potential role of mifepristone as a dexa methasone antagonist in the eye remains unanswered.…”

“…Confirmation was made, by direct assay of radiolabeled material, of a pharmacologically active dose within the aqueous humor and ocular tissues [3], This compound has been shown to have excellent steroid antagonism in nonocular systems, es pecially against progesterone and dexameth asone [4][5][6][7][8][9]. In the eye, mifepristone antago nized the IOP elevation caused by progester one [10], although anomalous results were obtained when mifepristone was tested against dexamethasone in albino rabbits [11], In the latter study, a variable response was obtained to topical dexamethasone, making assessment of any antagonism by mifepristone difficult.…”

Corticosteroid-induced glaucoma: a review of the literature

“…Mifepristone (RU 486-6), a peripheral progesterone blocker with antiglucocorticoid properties, has been shown to reduce IOP in both normotensive 76 and corticosteroid-induced ocular hypertensive rabbits. 77 However, this mode of therapy has not yet been used in human subjects. Southren et al 78,79 have inhibited dexamethasoneinduced ocular hypertension in rabbits using tetrahydrocortisol.…”

Influence of Serum Levels of Sex Hormones on Intraocular Pressure in Menopausal Women

“…16 Similarly, topical administration of progesterone has been reported to increase IOP in rabbit eyes. 17 Ziai et al 10 reported that changes in IOP observed during pregnancy were associated with serum levels of progesterone. However, attempts to correlate endogenous levels of sex hormones (estrogen, progesterone, testosterone, FSH, and LH) during phases of the menstrual cycle and aqueous hemodynamics failed to demonstrate any significant associations.…”