Direct effects of muscarinic agents on the outflow pathways in human eyes

PURPOSE. Recent studies demonstrating the presence of muscarinic receptors and contractile-like cells in the trabecular meshwork tissue and/or cell cu ltures from human eyes suggest the possibility that there may be a direct e ffect of muscarinic agonists on outflow facility. The present studies were conducted to determine whether muscarinic agonists could change outflow fac ility in perfused human ocular anterior segments, which lack an intact cili ary muscle. METHODS. Human eyes were dissected and perfused according to previously des cribed methods. A steady state baseline facility was established for 90 min utes, after which up to four sequential concentrations ranging from 10(-9) to 10(-3) M of pilocarpine, aceclidine, or carbachol were added to the perf usion medium. In other studies, 10(-6) M atropine was perfused alone follow ed by 10(-7) M carbachol with 10(-6) M atropine, whereas fellow control eye s received carbachol alone. Outflow facility was measured for GO minutes af ter each drug addition. The outflow facility measurement in each eye after drug administration was compared with the baseline measurement. RESULTS. Outflow facility increased from baseline facility in eyes treated with pilocarpine, aceclidine, or carbachol at lower concentrations (10(-9) to 10(-6) M) but remained unchanged at higher concentrations (10(-4) to 10( -2) M). The effects of carbachol at 10(-7) M were completely blocked by atr opine. CONCLUSIONS. Muscarinic agonists increase outflow facility in human eyes by a direct stimulation of the outflow tissues in the absence of an intact ci liary muscle. This effect is biphasic, occurring at concentrations of 10(-6 ) M and lower with no effect at higher concentrations.