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

Low doses (10(-9)-10(-6) M) of pilocarpine reportedly increase outflow facility in the organ-cultured human eye, suggesting a direct action on the trabecular meshwork. M3 muscarinic receptors have been found in both cultured human trabecular meshwork cells and tissue. We determined whether low pilo doses would increase outflow facility in the living monkey. The anterior chambers of both eyes of 17 pentobarbital anesthetized cynomolgus monkeys were cannulated and outflow facility measured bilaterally by 2-level constant pressure perfusion after an initial 2 ml exchange with Bárány's perfusand containing 24.5 microM phenylephrine (PE). Two subsequent exchanges were performed with one eye receiving Bárány's + PE + 10(-10)-10(-4) M pilocarpine and the contralateral eye receiving only Bárány's + PE. Outflow facility was measured for 35-40 min following each exchange. Accommodation and pupil diameter were measured before each exchange and approximately every 10 min during facility measurements. Outflow facility was significantly increased by 154 and 313% in eyes treated with 10(-5) M and 10(-4) M pilocarpine, respectively, related to contralateral 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 < or = 0.001) and 10(-4) M (accommodation, 10.6 +/- 0.0 diopters, P < or = 0.02; miosis, -3.4 +/- 1.0 mm, P < or = 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 human eye, nor do they induce miosis or accommodation. All three parameters respond to pilocarpine at similar doses, and there is no functional evidence of a meaningful outflow facility-relevant pilocarpine effect on the trabecular meshwork at doses lower than those which affect the ciliary muscle.