The effects of dexamethasone on fibronectin expression in cultured human trabecular meshwork cells.
Topical administration of glucocorticoids to the eye can lead to the development of ocular hypertension. This increase in intraocular pressure is caused by the heightened resistance to flow of aqueous humor from the eye, presumably at the trabecular meshwork (TM). This study reports the effects of dexamethasone (DEX) on the expression of the extracellular matrix protein fibronectin (FN) in cultured human TM cells (HTM). The expression of FN was evaluated in four HTM cell strains by epifluorescence microscopy and immunoblotting and autofluorography of electrophoretically separated cell proteins. There was a heterogeneous response of the four cell strains tested. Treatment of cell strain HTM4 with DEX (10(-7) mol/l) for 17 d caused an approximate doubling of cell-associated and secreted FN. This DEX-induced increase in FN expression was progressive after the first 7 d of treatment and was blocked partially with a glucocorticoid antagonist, cortexolone. By contrast, DEX treatment induced an intermediate 50-60% increase in FN expression in cell strains HTM10 and HTM2; in HTM6, FN was unchanged after exposure to the glucocorticoid. This model system may be useful to examine molecular changes associated with corticosteroid-induced ocular hypertension and evaluate glaucomatous changes in the TM because increased FN deposition occurs in the aqueous humor outflow pathway of patients with open-angle glaucoma.
Steely
H T
HT
Department of Glaucoma Research, Alcon Laboratories, Fort Worth, Texas 76134.
Browder
S L
SL
Julian
M B
MB
Miggans
S T
ST
Wilson
K L
KL
Clark
A F
AF
D000293:Adolescent; D000368:Aged; D000911:Antibodies, Monoclonal; D002460:Cell Line; D002478:Cells, Cultured; D003350:Cortodoxone / Q000494:pharmacology; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000187:drug effects; D005353:Fibronectins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005901:Glaucoma / Q000188:drug therapy; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010641:Phenotype; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D003907:Dexamethasone; D003350:Cortodoxone