The role of endogenous prostaglandins in clinically-used and investigational glaucoma therapy

Abstract

A review of the relevant literature strongly suggests that several medical and laser treatments presently used in glaucoma therapy, and other potential treatments under investigation, reduce IOP, at least, in part, by stimulating endogenous PG synthesis. There are four lines of evidence leading to this conclusion. (1) PGs are potent ocular hypotensive agents. (2) Adrenergic and cholinergic agonists stimulate PG synthesis by ocular tissues in vitro. (3) Epinephrine and ALT cause elevation of PG levels in the aqueous humor in vivo. (4) PG synthesis inhibitors such as indomethacin or flurbiprofen block, or partially inhibit, the reduction of IOP produced by epinephrine, para-aminoclonidine, forskolin, vanadate, verapamil, arachidonic acid, and ALT in rabbits, cats, monkeys, and/or humans. This last finding has great clinical importance with regard to the efficacy of such treatment modalities as epinephrine and ALT, since it indicates that these modalities may be less effective in reducing IOP in glaucoma patients who are taking systemic PG synthesis inhibitors - such as aspirin or indomethacin - for arthritis, cerebrovascular disease, arteriosclerotic coronary vascular disease, headache, or the common cold. Other surgical procedures for glaucoma such as cyclocryotherapy or other cyclodestructive procedures may also reduce IOP in part by stimulating local PG synthesis. Since PGs are produced in various ocular tissues and some of these PGs are highly potent ocular hypotensive agents, their potential role in mediating the reduction of IOP produced by medical or surgical modalities of glaucoma therapy must always be considered. Furthermore, these considerations support the concept that topical application of an appropriately selected PG, or its derivative, may provide a more direct means of lowering IOP than some of the currently used procedures or therapeutic agents.