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John Stokes, June Noble, Lawrence Brett, Calbert Phillips, Jonathan R. Seckl, Colm O’Brien, Ruth Andrew; Distribution of Glucocorticoid and Mineralocorticoid Receptors and 11β-Hydroxysteroid Dehydrogenases in Human and Rat Ocular Tissues. Invest. Ophthalmol. Vis. Sci. 2000;41(7):1629-1638.
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purpose. The administration of glucocorticoids as topical or systemic
medications may lead to the development of ocular hypertension through
the induction of morphologic and biochemical changes in the trabecular
meshwork leading to a reduction in the facility of aqueous outflow.
Glucocorticoids exert their physiological effects by binding to and
activating glucocorticoid and mineralocorticoid receptors. The activity
of glucocorticoids is critically regulated at a prereceptor level by
the two isozymes of 11β-hydroxysteroid dehydrogenase. The purpose of
this study was to determine the distribution of glucocorticoid target
receptors and the isozymes of 11β-hydroxysteroid dehydrogenase (11β
-HSD) that regulate the activity of glucocorticoids at a prereceptor
level in human and rat ocular tissues.
methods. Horizontal sections of normal adult human and rat eyes were cut and
hybridized with 35S-labeled cRNA probes specific for the
glucocorticoid receptor, mineralocorticoid receptor, and 11β-HSD
types 1 and 2 using in situ hybridization. Immunohistochemical analysis
of glucocorticoid and mineralocorticoid receptors using monoclonal
antibodies was carried out on rat eye tissue sections. Whole rat eyes
were homogenized and the activity of 11β-HSD types 1 and 2 in the eye
assessed as the percentage conversion of tritiated corticosterone to
tritiated 11-dehydrocorticosterone when corticosterone was added to the
results. In the rat ocular tissues mRNAs encoding glucocorticoid receptor,
mineralocorticoid receptor, and 11β-HSD types 1 and 2 were detected
in nonpigmented ciliary epithelium, trabecular meshwork, corneal
epithelium and endothelium, and anterior lens epithelium.
Immunohistochemistry confirmed the presence of glucocorticoid and
mineralocorticoid receptors at these sites. Activity of both isozymes
of 11β-HSD was demonstrated in homogenized rat eyes (percentage
conversion of tritiated corticosterone to 11-dehydrocorticosterone;
mean ± SD, 11β-HSD 1 = 15% ± 5.3%, 11β-HSD 2 =
7.9% ± 2.8%). In both human and rat eyes, expression of mRNAs
encoding glucocorticoid receptor and 11β-HSD type 1 was high in the
trabecular meshwork and lens epithelium, whereas expression of mRNAs
encoding the mineralocorticoid receptor and 11β-HSD type 2 was high
in nonpigmented ciliary epithelium and corneal epithelium and
conclusions. Glucocorticoid target receptors and the enzymes regulating
glucocorticoid activity at these receptors are present in mammalian
ocular tissues, which regulate aqueous humor formation and outflow.
Alteration in the number or affinity of receptors or in the activity of
regulatory enzymes may alter the susceptibility of certain individuals
to the effects of glucocorticoids on intraocular
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