Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular meshwork cells.

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Abstract

PURPOSE: To determine the effects of glucocorticoid treatment on the microfilament structure of cultured human trabecular meshwork cells. Topical or systemic administration of glucocorticoids can lead to the development of ocular hypertension and to the development of vision loss, which is clinically similar to primary open angle glaucoma. However, the mechanism(s) by which glucocorticoids cause ocular hypertension is not well defined. Alterations in the trabecular meshwork, the site of drainage of aqueous humor from the eye, have been linked to the development of ocular hypertension. METHODS: Human trabecular meshwork cells were cultured in the presence and absence of glucocorticoids for 0 to 21 days. The microfilament organization of the cultured trabecular meshwork cells was examined by epifluorescent and transmission electron microscopy. RESULTS: Glucocorticoids caused a progressive change in the organization of microfilaments in the trabecular meshwork cells, but not in other cultured ocular cells. By fluorescence microscopic analysis, the actin stress fibers found in control trabecular meshwork cells were reorganized on treatment with glucocorticoids into cross-linked actin networks that resembled geodesic-dome-like polygonal lattices. The cross-linked actin networks were reversible on withdrawal of the glucocorticoid treatment. Dose-response data for dexamethasone, relative ranking of activity with glucocorticoid potency, and partial inhibition with glucocorticoid antagonists all suggest the involvement of the trabecular meshwork glucocorticoid receptor in cross-linked actin network formation. The reorganization of the trabecular meshwork cytoskeleton alters cell function because glucocorticoid treatment of cultured trabecular meshwork cells also inhibited trabecular meshwork cell migration and proliferation. CONCLUSION: The steroid-induced alteration in trabecular meshwork cytoskeleton may be an important factor in the development of steroid-induced ocular hypertension and may play a role in the ocular hypertension associated with primary open angle glaucoma.