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 model system in which to study glaucomatous damage to the trabecular meshwork. One of the most important risk factors for glaucoma is an elevated intraocular pressure. The administration of glucocorticoids also can cause elevated intraocular pressure in some individuals. In addition, there is suggestive evidence linking glucocorticoids with the development of glaucoma. Glucocorticoids cause multiple effects on the human trabecular meshwork including changes in extracellular matrix metabolism, organisation of the cytoskeleton, and changes in gene expression and cell function. New discoveries on the molecular mechanisms of glucocorticoid receptor action provide new opportunities to study the possible role of this receptor in the development of glaucoma. For example, alternate spliced forms of the glucocorticoid receptor, glucocorticoid receptor response element half-sites, numerous modulatory factors, and direct effects of nuclear transcription factors have been recently described. Other recent information has shown that the new glaucoma gene (GLC1A/myocilin) is induced in the human trabecular meshwork by glucocorticoids. Although the exact function of myocilin is currently unknown, it offers the opportunity to dissect the molecular pathways regulating aqueous humor outflow. Future challenges include determining (1) which glucocorticoid effects in the human trabecular meshwork are responsible for elevated intraocular pressure; and (2) the significance of these findings to the development of glaucoma.
Wordinger
R J
RJ
Department of Anatomy and Cell Biology, University of North Texas, Health Science Center, Fort Worth 76107, USA. rwording@hsc.unt.edu
Clark
A F
AF
D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005902:Glaucoma, Open-Angle / Q000139:chemically induced* / Q000235:genetics; D005938:Glucocorticoids / Q000009:adverse effects* / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D009798:Ocular Hypertension / Q000139:chemically induced / Q000235:genetics; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099179:Myocilin
D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D014157:Transcription Factors; D000099179:Myocilin