Hewison, Martin

Murray, Philip

Rauz, Saaeha

Shackleton, CHL

Stewart, Paul

Walker, Elizabeth

Wood, PJ

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 11 beta -hydroxy-steroid dehydrogenase (11 beta -HSD) isozymes: an oxo-reductase (11 beta -HSD1) that activates cortisol (F) from cortisone (E) and a dehydrogenase (11 beta -HSD2) that inactivates F to E. The purpose of this study was to analyze the expression and putative role of 11 beta -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 11 beta -HSD. RESULTS. 11 beta -HSD1 was expressed in the basal cells of the corneal epithelium and the NPE. 11 beta -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 11 beta -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 11 beta -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 &lt;0.0001 and 11.78 +/- 1.50 min Hg, P &lt;0.0001, respectively). CONCLUSIONS. These results suggest that the 11 beta -HSD1 isozyme may modulate steroid-regulated sodium transport across the NPE, thereby influencing IOP

Expression and putative role of 11beta-hydroxysteroid dehydrogenase isozymes within the human eye

Abstract

Similar works

Full text

Available Versions

University of Birmingham Research Portal

University of Birmingham Research Portal