PGF_2α/pilocarpine interactions on IOP and accommodation in monkeys

We investigated whether (i) single or repeated topical treatment with either the tromethamine salt or the isopropyl ester of prostaglandin F_2α(PGF_2α-TS or PGF_2α-IE) inhibits the accommodative response to pilocarpine; (ii) pilocarpine given after PGF_2α inhibits the latter’s ocular hypotensive effect, as occurs with the reverse order of administration. PGF_2α-IE (2 μg) or PGF_2α-TS (50 μg) was applied topically to the right eye of five cynomolgus monkeys twice daily for 4 days. Before initial dosing, and 1 hr after the initial and final dose the animals were anesthetized with ketamine, and intraocular pressure (IOP) and refraction determined bilaterally. Following post-PG IOP and refraction determinations, pilocarpine HCl was given topically (bilaterally) or infused i.m. over 10 min, after which refraction was determined periodically for 50 min. IOP was then again determined. After a single unilateral dose of PGF_2α-TS or PGF_2α-IE, IOP was unchanged. Both eyes accommodated markedly and equally in response to pilocarpine, and IOP fell bilaterally by a statistically significant 3 mmHg in response to pilocarpine. Repeated doses of PGF_2α-TS or PGF_2α-IE did not significantly affect the accommodative response to pilocarpine, while pilocarpine did not alter the ∼ 10 mmHg ipsilateral IOP fall induced by repeated dosing of PGF_2α-TS or PGF_2α-IE. It is concluded that repeated unilateral topical application of PGF_2α-TS or PGF_2α-IE to the cynomolgus monkey eye markedly reduces ipsilateral IOP, but has no effect on the ipsilateral or contralateral eye accommodative response to pilocarpine. Pilocarpine reverses the PGF_2α-TS or PGF_2α-IE-induced fall in IOP when given before the PGF_2α, but does not prevent it when given after, within the parameters of this study.