IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stokes, J.
Right arrow Articles by Andrew, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stokes, J.
Right arrow Articles by Andrew, R.
(Investigative Ophthalmology and Visual Science. 2000;41:1629-1638.)
© 2000 by The Association for Research in Vision and Ophthalmology, Inc.

Distribution of Glucocorticoid and Mineralocorticoid Receptors and 11ß-Hydroxysteroid Dehydrogenases in Human and Rat Ocular Tissues

John Stokes1,2, June Noble1, Lawrence Brett1, Calbert Phillips2, Jonathan R. Seckl1, Colm O’Brien3 and Ruth Andrew1

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

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 11ß-hydroxysteroid dehydrogenase. The purpose of this study was to determine the distribution of glucocorticoid target receptors and the isozymes of 11ß-hydroxysteroid dehydrogenase (11 ß-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 11ß-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 11ß-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 homogenate.

RESULTS. In the rat ocular tissues mRNAs encoding glucocorticoid receptor, mineralocorticoid receptor, and 11ß-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 11ß-HSD was demonstrated in homogenized rat eyes (percentage conversion of tritiated corticosterone to 11-dehydrocorticosterone; mean ± SD, 11ß-HSD 1 = 15% ± 5.3%, 11ß-HSD 2 = 7.9% ± 2.8%). In both human and rat eyes, expression of mRNAs encoding glucocorticoid receptor and 11ß-HSD type 1 was high in the trabecular meshwork and lens epithelium, whereas expression of mRNAs encoding the mineralocorticoid receptor and 11ß-HSD type 2 was high in nonpigmented ciliary epithelium and corneal epithelium and endothelium.

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 pressure.




This article has been cited by other articles:


Home page
 IOVSHome page
V. Gupta, N. Awasthi, and B. J. Wagner
Specific Activation of the Glucocorticoid Receptor and Modulation of Signal Transduction Pathways in Human Lens Epithelial Cells
Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1724 - 1734.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
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]

Home page
 J EndocrinolHome page
N. Draper and P. M Stewart
11{beta}-Hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action
J. Endocrinol., August 1, 2005; 186(2): 251 - 271.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Ophthalmol.Home page
M J S Langman, R J Lancashire, K K Cheng, and P M Stewart
Systemic hypertension and glaucoma: mechanisms in common and co-occurrence
Br. J. Ophthalmol., August 1, 2005; 89(8): 960 - 963.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. W. Tomlinson, E. A. Walker, I. J. Bujalska, N. Draper, G. G. Lavery, M. S. Cooper, M. Hewison, and P. M. Stewart
11{beta}-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response
Endocr. Rev., October 1, 2004; 25(5): 831 - 866.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. Stokes, B. R. Walker, J. C. Campbell, J. R. Seckl, C. O'Brien, and R. Andrew
Altered Peripheral Sensitivity to Glucocorticoids in Primary Open-Angle Glaucoma
Invest. Ophthalmol. Vis. Sci., December 1, 2003; 44(12): 5163 - 5167.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
E. R. James, L. Robertson, E. Ehlert, P. Fitzgerald, N. Droin, and D. R. Green
Presence of a Transcriptionally Active Glucocorticoid Receptor {alpha} in Lens Epithelial Cells
Invest. Ophthalmol. Vis. Sci., December 1, 2003; 44(12): 5269 - 5276.
[Abstract] [Full Text] [PDF]

Home page
 QJMHome page
S. Rauz, C.M.G. Cheung, P.J. Wood, M. Coca-Prados, E.A. Walker, P.I. Murray, and P.M. Stewart
Inhibition of 11{beta}-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension
QJM, July 1, 2003; 96(7): 481 - 490.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
V. Gupta and B. J. Wagner
Expression of the Functional Glucocorticoid Receptor in Mouse and Human Lens Epithelial Cells
Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 2041 - 2046.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
S. Rauz, E. A. Walker, S. V. Hughes, M. Coca-Prados, M. Hewison, P. I. Murray, and P. M. Stewart
Serum- and Glucocorticoid-Regulated Kinase Isoform-1 and Epithelial Sodium Channel Subunits in Human Ocular Ciliary Epithelium
Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1643 - 1651.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Le Menuet, R. Isnard, M. Bichara, S. Viengchareun, M. Muffat-Joly, F. Walker, M.-C. Zennaro, and M. Lombes
Alteration of Cardiac and Renal Functions in Transgenic Mice Overexpressing Human Mineralocorticoid Receptor
J. Biol. Chem., October 12, 2001; 276(42): 38911 - 38920.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
S. Rauz, E. A. Walker, C. H. L. Shackleton, M. Hewison, P. I. Murray, and P. M. Stewart
Expression and Putative Role of 11{beta}-Hydroxysteroid Dehydrogenase Isozymes within the Human Eye
Invest. Ophthalmol. Vis. Sci., August 1, 2001; 42(9): 2037 - 2042.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2000 by the Association for Research in Vision and Ophthalmology