Substantial evidence indicates that a single topical application of prostaglandins (PGs) can reduce intraocular pressure (IOP) in the eyes of several species. However, earlier literature, dealing with ocular hypertensive and inflammatory responses, shows the development of tachyphylaxis to subsequent doses of PGs. If similar tolerance developed to the ocular hypotensive effects of PGs, it would preclude the use of these agents in the treatment of chronic glaucoma. The present study shows, however, that although tachyphylaxis to the ocular hypotensive effects of PGs develops in rabbits, this is not a typical response among mammals. Significant IOP reduction was maintained in cats for up to 9 months by topical application of PGE 2 at 12-, 24-, or 48-hr intervals. The IOP reduction was jeopardized seriously only when the PG was applied every other day for several days or when, on a few occasions, 3 days were allowed to elapse between PGE 2 applications. Ocular hypotension was also maintained during the course of topical treatment of rhesus monkey eyes with PGF 2a . Short periods of pupillary constriction followed the application of each dose of PGF 2a to cat eyes, but the miotic response of rhesus monkeys to PGF 2a and cats to PGE 2 was negligible. Other apparent side effects were noted, but none of these were severe or progressive. These results clearly demonstrate that tachyphylaxis, or tolerance, is not expected to present an obstacle to the development of eicosanoids and/or their derivatives as therapeutic agents for the long-term treatment of ocular hypertension and chronic glaucoma. Invest Ophthalmol Vis Sci 24: [312][313][314][315][316][317][318][319] 1983 Early studies on the effects of prostaglandins (PGs) on the eye, primarily designed to determine the role of these autacoids in the ocular irritative response, concluded that exogenous PGs can produce increased intraocular pressure (IOP) and breakdown of the blood-aqueous barrier. 1 It has recently been shown, however, that appropriate doses of PGF 2a topically applied to the eyes of rabbits, 2 owl monkeys, 3 rhesus monkeys, and cats 4 can, in fact, reduce rather than increase IOP. In the rabbit there is only a narrow margin between the hypotensive dose of PGF 2a and a dose that causes initial hypertension. 2 Ten-to 100-fold higher PGF 2a doses than those that reduce IOP in the rabbit are required to produce the same effect in owl monkeys, rhesus monkeys, and cats, but eve
