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Low doses of pilocarpine do not significantly increase outflow facility in the cynomolgus monkey
J A Kiland1, W C Hubbard, P L Kaufman
1Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, USA.
Abstract:
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.
Insights
Low-dose pilocarpine did not increase outflow facility in living monkeys, unlike in organ cultures. Higher doses caused effects, but not at levels below those impacting the ciliary muscle.
Area of Science:
- Ophthalmology
- Pharmacology
- Physiology
Background:
- Low-dose pilocarpine (10⁻⁹–10⁻⁶ M) reportedly enhances outflow facility in organ-cultured human eyes.
- This suggests a direct effect on the trabecular meshwork, supported by the presence of M3 muscarinic receptors.
- The study investigates if these low pilocarpine doses yield similar results in living primate eyes.
Purpose of the Study:
- To determine if low pilocarpine doses increase outflow facility in living cynomolgus monkeys.
- To assess pilocarpine's effects on accommodation and pupil diameter at similar concentrations.
- To compare findings in vivo with previous organ-cultured human eye studies.
Main Methods:
- Cynomolgus monkeys underwent bilateral anterior chamber cannulation for outflow facility measurement.
- Constant pressure perfusion was used after perfusate exchange with phenylephrine (PE) and varying pilocarpine concentrations (10⁻¹⁰–10⁻⁴ M).
- Accommodation and pupil diameter were measured concurrently.
Main Results:
- Outflow facility significantly increased only at high pilocarpine doses (10⁻⁵ M and 10⁻⁴ M) compared to controls.
- Accommodation and miosis were induced at these higher doses (10⁻⁵ M and 10⁻⁴ M).
- Low pilocarpine doses (below 10⁻⁵ M) did not increase outflow facility, induce miosis, or cause accommodation.
Conclusions:
- Low anterior chamber pilocarpine doses do not enhance outflow facility in living monkeys.
- The observed effects in organ cultures were not replicated in vivo at similar concentrations.
- Functional evidence for a trabecular meshwork pilocarpine effect at low doses is lacking; effects require higher doses impacting the ciliary muscle.