Distribution of glucocorticoid and mineralocorticoid receptors and 11 beta-hydroxysteroid dehydrogenases in human and rat ocular tissues

PURPOSE. The administration of glucocorticoids as topical or systemic medic ations may lead to the development of ocular hypertension through the induc tion of morphologic and biochemical changes in the trabecular meshwork lead ing to a reduction in the facility of aqueous outflow. Glucocorticoids exer t their physiological effects by binding to and activating glucocorticoid a nd mineralocorticoid receptors. The activity of glucocorticoids is critical ly regulated at a prereceptor level by the two isozymes of 11 beta-hydroxys teroid dehydrogenase. The purpose of this study was to determine the distri bution of glucocorticoid target receptors and the isozymes of 11 beta-hydro xysteroid dehydrogenase (11 beta-HSD) that regulate the activity of glucoco rticoids at a prereceptor level in human and rat ocular tissues. METHODS. Horizontal sections of normal adult human and rat eyes were cut an d hybridized with S-35-labeled cRNA probes specific for the glucocorticoid receptor, mineralocorticoid receptor, and 11 beta-HSD types 1 and 2 using i n situ hybridization. Immunohistochemical analysis of glucocorticoid and mi neralocorticoid receptors using monoclonal, antibodies was carried out on r at eye tissue sections. Whole rat eyes were homogenized and the activity of 11 beta-HSD types 1 and 2 in the eye assessed as the percentage conversion of tritiated corticosterone to tritiated Il-dehydrocorticosterone when cor ticosterone was added to the homogenate. RESULTS. in the rat ocular tissues mRNAs encoding glucocorticoid receptor, mineralocorticoid receptor, and 11 beta-HSD types 1 and 2 were detected in nonpigmented ciliary epithelium, trabecular meshwork, corneal epithelium an d endothelium, and anterior lens epithelium. Immunohistochemistry confirmed the presence of glucocorticoid and mineralocorticoid receptors at these si tes. Activity of both isozymes of 11 beta-HSD was demonstrated in homogeniz ed rat eyes (percentage conversion of tritiated corticosterone to 11-dehydr ocorticosterone; mean +/- SD, 11 beta-HSD 1 = 15% +/- 5.3%, 11 beta-HSD 2 = 7.9% +/- 2.8%). In both human and rat eyes, expression of mRNAs encoding g lucocorticoid receptor and 11 beta-HSD type 1 was high in the trabecular me shwork and lens epithelium, whereas expression of mRNAs encoding the minera locorticoid receptor and 11 beta-HSD type 2 was high in nonpigmented ciliar y epithelium and corneal epithelium and endothelium. CONCLUSIONS. Glucocorticoid target receptors and the enzymes regulating glu cocorticoid activity at these receptors are present in mammalian ocular tis sues, which regulate aqueous humor formation and outflow. Alteration in, th e number or affinity of receptors or in the activity of regulatory enzymes may alter the susceptibility of certain individuals to the effects of gluco corticoids on intraocular pressure.