Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension

• Published in: QJM : An International Journal of Medicine 2003-07, Vol.96 (7), p.481-490
• Main Authors: Rauz, S, Cheung, C M G, Wood, P J, Coca-Prados, M, Walker, E A, Murray, P I, Stewart, P M
• Format: Article
• Language: English
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 2; Aged; Aqueous Humor - chemistry; Aqueous Humor - enzymology; Carbenoxolone - pharmacology; Cortisone - analysis; Double-Blind Method; Enzyme Inhibitors - therapeutic use; Female; Humans; Hydrocortisone - analysis; Hydroxysteroid Dehydrogenases - antagonists & inhibitors; Intraocular Pressure - drug effects; Male; Mineralocorticoid Receptor Antagonists; Ocular Hypertension - drug therapy; Ocular Hypertension - physiopathology; Prospective Studies; Receptors, Glucocorticoid - antagonists & inhibitors
• ISSN: 1460-2725

Intraocular pressure (IOP) is maintained by a balance between aqueous humour (AH) production (dependent on sodium transport across a ciliary epithelial bi-layer) and drainage (predominantly through the trabecular meshwork). In peripheral epithelial tissues, sodium and water transport is regulated by corticosteroids and the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes (11beta-HSD1 activating cortisol from cortisone, 11beta-HSD2 inactivating cortisol to cortisone). To analyse expression of 11beta-HSD in the human eye and investigate its putative role in AH formation. Multipart prospective study, including a randomized controlled clinical trial. The expression of 11beta-HSD1 in normal human anterior segments was evaluated by in situ hybridization (ISH). RT-PCR for 11beta-HSDs, glucocorticoid and mineralocorticoid receptors (GR, MR) was performed on human ciliary body tissue. AH cortisol and cortisone concentrations were measured by radioimmunoassay on specimens taken from patients with primary open-angle glaucoma (POAG) and age-matched controls. Randomized, placebo-controlled studies of healthy volunteers and patients with ocular hypertension (OHT, raised IOP but no optic neuropathy) assessed the effect of oral carbenoxolone (CBX, an inhibitor of 11beta-HSD) on IOP. ISH defined expression of 11beta-HSD1 in the ciliary epithelium, while RT-PCR analysis of ciliary body tissue confirmed expression of 11beta-HSD1, with additional GR and MR, but not 11beta-HSD2 expression. In both POAG patients and controls, AH concentrations of cortisol exceeded those of cortisone. The CBX-treated healthy volunteers who demonstrated the largest change in urinary cortisol metabolites, indicative of 11beta-HSD1 inhibition, had the greatest fall in IOP. Patients with OHT showed an overall reduction of IOP by 10% following CBX administration, compared to baseline (p