Low doses of pilocarpine do not significantly increase outflow facility inthe cynomolgus monkey

Low doses (10(-9)-10(-6) M) of pilocarpine reportedly increase outflow faci lity in the organ-cultured human eye, suggesting a direct action on the tra becular meshwork. M-3 muscarinic receptors have been found in both cultured human trabecular meshwork cells and tissue. We determined whether low pile doses would increase outflow facility in the living monkey. The anterior chambers of both eyes of 17 pentobarbital anesthetized cynomol gus monkeys were cannulated and outflow facility measured bilaterally by 2- level constant pressure perfusion after an initial 2 ml exchange with Baran y's perfusand containing 24.5 mu M phenylpherine (PE). Two subsequent excha nges were performed with one eye receiving Barany's + PE + 10(-10)-10(-4) M pilocarpine and the contralateral eye receiving only Barany's + PE, Outflo w facility was measured for 35-40 min following each exchange. Accommodatio n and pupil diameter were measured before each exchange and approximately e very 10 min during facility measurements. Outflow facility was significantly increased by 154 and 313 % in eyes treat ed with 10(-5) M and 10(-4) M pilocarpine, respectively, related to contral ateral controls. Accommodation and miosis also were induced only at 10(-5) M (accommodation, 3.3 +/- 1.6 diopters, NS; miosis, -4.1 +/- 0.5 mm, P less than or equal to 0.001) and 10(-4) M (accommodation, 10.6 +/- 0.0 diopters , P less than or equal to 0.02; miosis, -34 +/- 1.0 mm, P less than or equa l to 0.025) pilocarpine. We conclude that low anterior chamber doses of pilocarpine do not increase outflow facility in the living monkey as reported in the organ-cultured hum an eye, nor do they induce miosis or accommodation. All three parameters re spond to pilocarpine at similar doses, and there is no functional evidence of a meaningful outflow facility-relevant pilocarpine effect on the trabecu lar meshwork at doses lower than those which affect the ciliary muscle. (C) 2000 Academic Press.