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1 From the Academic Unit of Ophthalmology, Division of Immunity and Infection, and 2 Department of Endocrinology, Division of Medical Sciences, University of Birmingham, United Kingdom; and 3 Mass Spectrometry Facility, Children’s Hospital Oakland Research Institute, California.
PURPOSE. The human eye is an important target tissue for steroid hormones, and glucocorticoids have been implicated in the pathogenesis of ocular disease, including glaucoma. In peripheral tissues, corticosteroid hormone action is regulated at a prereceptor level through the activity of the 11ß-hydroxysteroid dehydrogenase (11ß-HSD) isozymes: an oxo-reductase (11ß-HSD1) that activates cortisol (F) from cortisone (E) and a dehydrogenase (11ß-HSD2) that inactivates F to E. The purpose of this study was to analyze the expression and putative role of 11ß-HSD within the human eye.
METHODS. Immunohistochemical and reverse transcription–polymerase chain reaction (RT-PCR) studies were performed on sections of human ocular tissues, surgical trabecular meshwork (TM) specimens and a ciliary nonpigmented epithelial (NPE) cell-line. Free F and E concentrations in aqueous humor were determined by gas chromatography-mass spectrometry (GC/MS). IOP was measured in eight male volunteers before and after oral ingestion of carbenoxolone (CBX), a known inhibitor of 11ß-HSD.
RESULTS. 11ß-HSD1 was expressed in the basal cells of the corneal epithelium and the NPE. 11ß-HSD2 was restricted to the corneal endothelium. RT-PCR revealed mRNA for only the glucocorticoid receptor (GR) in the TM specimens, whereas GR, mineralocorticoid receptor and 11ß-HSD1 mRNAs were all present in the NPE cell line. The demonstration of free F in excess of E (F/E 14:1) in the aqueous humor suggested predominant 11ß-HSD1 activity. Compared with baseline (14.7 ± 1.06 mm Hg, mean ± SD), the IOP decreased significantly on both the third and seventh days of CBX ingestion (12.48 ± 1.11 mm Hg, P < 0.0001 and 11.78 ± 1.50 mm Hg, P < 0.0001, respectively).
CONCLUSIONS. These results suggest that the 11ß-HSD1 isozyme may modulate steroid-regulated sodium transport across the NPE, thereby influencing IOP.
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