Effects of glucocorticoids on the trabecular meshwork: Towards a better understanding of glaucoma

Glucocorticoid effects on the human trabecular meshwork can be used as a mo del system in which to study glaucomatous damage to the trabecular meshwork . One of the most important risk factors for glaucoma is an elevated intrao cular pressure. The administration of glucocorticoids also can cause elevat ed intraocular pressure in some individuals. In addition, there is suggesti ve evidence linking glucocorticoids with the development of glaucoma. Gluco corticoids cause multiple effects on the human trabecular meshwork includin g changes in extracellular matrix metabolism, organisation of the cytoskele ton, and changes in gene expression and cell function. New discoveries on t he molecular mechanisms of glucocorticoid receptor action provide new oppor tunities to study the possible role of this receptor in the development of glaucoma. For example, alternate spliced forms of the glucocorticoid recept or, glucocorticoid receptor response element half-sites, numerous modulator y factors, and direct effects of nuclear transcription factors have been re cently described. Other recent information has shown that the new glaucoma gene (GLC1A/myocilin) is induced in the human trabecular meshwork by glucoc orticoids. Although the exact function of myocilin is currently unknown, it offers the opportunity to dissect the molecular pathways regulating aqueou s humor outflow. Future challenges include determining (1) which glucocorti coid effects in the human trabecular meshwork are responsible for elevated intraocular pressure; and (2) the significance of these findings to the dev elopment of glaucoma. (C) 1999 Elsevier Science Ltd. All rights reserved.