Mechanism of Action of a New Glaucoma Drug

The demonstration of the ocular hypotensive activity of the cortisol metabolite 3a, 5ß-tetrahydrocortisol (3a, 5ß-THF) in rabbits made ocular hypertensive with glucocorticoids and in patients with primary open-angle glaucoma (POAG) indicates the necessity of elucidating the mechanism of action of this drug.

Hypotheses

It is hypothesized that 3a, 5ß-THF is a glucocorticoid antagonist.

Specific Aims

The specific aims of this project are to determine whether 3a, 5ß-THF interferes with agonist binding (and activation) of the glucocorticoid receptor in tissue involved in the regulation of intraocular pressure.

Progress To Date

Preliminary results indicate that 3a, 5ß-THF (1) does not compete with dexamethasone for binding to the glucocorticoid receptor and (2) does not accelerate the dissociation of dexamethasone from the receptor. These results are currently being confirmed and other types of interaction between 3a, 5ß-THF and the glucocorticoid receptor are being