HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stokes, J. Articles by Andrew, R. Search for Related Content PubMed PubMed Citation Articles by Stokes, J. Articles by Andrew, R.

Altered Peripheral Sensitivity to Glucocorticoids in Primary Open-Angle Glaucoma

¹From the Endocrinology Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, United Kingdom; the ²Department of Ophthalmology, Princess Alexandra Eye Pavilion, Edinburgh, Scotland, United Kingdom; and the ³Institute of Ophthalmology, Mater Hospital, Dublin, Ireland.

PURPOSE. Increased levels of glucocorticoids are associated with raised intraocular pressure (IOP). The activity of glucocorticoids is regulated at a prereceptor level by 11ß-hydroxysteroid dehydrogenases (11ß-HSD). This study was an investigation of the central and peripheral sensitivity to glucocorticoids in patients with POAG or ocular hypertension (OHT) and the differential metabolism of glucocorticoids by 11ß-HSDs.

METHODS. Patients with POAG or OHT and normal control subjects were studied. Peripheral sensitivity to glucocorticoids was assessed as dermal blanching and central sensitivity by dexamethasone suppression testing. Daily production rates of glucocorticoids were determined by quantifying metabolites in 24-hour urine. Plasma cortisol levels were determined at baseline (9 AM) and after an overnight low-dose dexamethasone suppression test. In a separate study, plasma and aqueous humor cortisol levels were determined in patients with POAG and normal subjects.

RESULTS. Patients with POAG exhibited a greater cutaneous vasoconstrictor response to glucocorticoids than patients with OHT and normal subjects (20.7 ± 3.1 vs. 8.5 ± 4.4 and 8.6 ± 4.5 arbitrary units, respectively; P < 0.05 in each case). Total glucocorticoid production rates were not different between groups, nor were total circulating cortisol levels before or after suppression of the hypothalamic-pituitary-adrenal axis by dexamethasone or concentrations in aqueous humor. The ratio of urinary cortisol to cortisone metabolites was elevated in POAG versus normal control and OHT (1.74 ± 0.13 vs. 1.34 ± 0.11 and 1.32 ± 0.14; P < 0.05 in each case), indicating a change in the balance of 11ß-HSDs, without a change in other metabolic pathways.

CONCLUSIONS. Patients with POAG exhibit increased peripheral vascular sensitivity to glucocorticoids. Increased sensitivity of glucocorticoid receptors, may enhance local glucocorticoid action in the eye and exacerbate the adverse effects of glucocorticoids in this condition

This article has been cited by other articles:

				C. U Onyimba, N. Vijapurapu, S J. Curnow, P. Khosla, P. M Stewart, P. I Murray, E. A Walker, and S. Rauz Characterisation of the prereceptor regulation of glucocorticoids in the anterior segment of the rabbit eye. J. Endocrinol., August 1, 2006; 190(2): 483 - 493. [Abstract] [Full Text] [PDF]

				X. Zhang, A. F. Clark, and T. Yorio Regulation of Glucocorticoid Responsiveness in Glaucomatous Trabecular Meshwork Cells by Glucocorticoid Receptor-{beta} Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4607 - 4616. [Abstract] [Full Text] [PDF]