Direct effects of muscarinic agents on the outflow pathways in human eyes.
OBJECTIVE
Recent studies demonstrating the presence of muscarinic receptors and contractile-like cells in the trabecular meshwork tissue and/or cell cultures from human eyes suggest the possibility that there may be a direct effect of muscarinic agonists on outflow facility. The present studies were conducted to determine whether muscarinic agonists could change outflow facility in perfused human ocular anterior segments, which lack an intact ciliary muscle.


METHODS
Human eyes were dissected and perfused according to previously described methods. A steady state baseline facility was established for 90 minutes, after which up to four sequential concentrations ranging from 10(-9) to 10(-3) M of pilocarpine, aceclidine, or carbachol were added to the perfusion medium. In other studies, 10(-6) M atropine was perfused alone followed by 10(-7) M carbachol with 10(-6) M atropine, whereas fellow control eyes received carbachol alone. Outflow facility was measured for 60 minutes after 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 atropine.


CONCLUSIONS
Muscarinic agonists increase outflow facility in human eyes by a direct stimulation of the outflow tissues in the absence of an intact ciliary muscle. This effect is biphasic, occurring at concentrations of 10(-6) M and lower with no effect at higher concentrations.
Erickson
K A
KA
Department of Ophthalmology, Boston University School of Medicine, Massachusetts 02118, USA. kerick@bu.edu
Schroeder
A
A
D000368:Aged; D000869:Anterior Eye Segment / Q000187:drug effects* / Q000378:metabolism; D001082:Aqueous Humor / Q000378:metabolism*; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D010862:Pilocarpine; C084650:aceclidine; D001285:Atropine; D002217:Carbachol