cortodoxone and Glaucoma

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.

Topics: Adolescent; Aged; Antibodies, Monoclonal; Cell Line; Cells, Cultured; Cortodoxone; Dexamethasone; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix; Fibronectins; Fluorescent Antibody Technique; Glaucoma; Humans; Immunoblotting; Microscopy, Fluorescence; Middle Aged; Phenotype; Trabecular Meshwork

Systemic absorption has been reported after the use of corticosteroid eye drops. Prolonged use could result in adrenocortical insufficiency and an associated adrenal crisis under stressful situations. For that reason, we studied the hypothalamic-pituitary-adrenal axis of patients receiving corticosteroid eye drope. Fifteen patients were given 0.1% dexamethasone sodium phosphate eye drops, one drop (approximately 1/30 ml) to each eye four times a day for six weeks. This dosage resulted in partial adrenal suppression, manifested by reduced levels of plasma cortisol. However, in each case, the hypothalamic-pituitary-adrenal axis, as evaluated with the use of the oral metyrapone tartrate test, was intact.

Topics: Administration, Topical; Cortodoxone; Dexamethasone; Glaucoma; Humans; Hydrocortisone; Hypothalamus; Intraocular Pressure; Metyrapone; Ophthalmic Solutions; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System