Variable Effects of Previously Untested Muscarinic Receptor Antagonists on Experimental Myopia

Abstract

Atropine, pirenzepine, and himbacine prevent form-deprivation myopia (FDM) when administered intravitreously. The mechanisms and sites of action of these drugs against myopia are not clear. To shed further light on whether this mechanism is muscarinic, several other muscarinic antagonists were tested. Various concentrations of atropine, pirenzepine, dexetimide, scopolamine, tropicamide, benztropine, dicyclomine, gallamine, mepenzolate, oxyphenonium, propantheline, procyclidine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), hexahydro-sila-difenidol (HHSiD), p-fluorohexahydro-sila-difenidol (pf-HHSiD), methoctramine, AFDX-116, and quinuclidinyl benzilate (QNB) were injected into goggled eyes of Leghorn cockerels three times at 48-hour intervals. Fellow control eyes received saline. Control animals received saline in both eyes. Twenty-four hours after final injections, refraction, eye weight, and axial length were measured, and eyes were prepared for microscopy. Other than atropine and pirenzepine, only oxyphenonium caused full rescue from FDM (goggled versus control; mean +/- SD; refraction differences: -9.50 +/- 0.22 D vs. 0.83 +/- 0.31 D, P < 0.001; wet weight differences: 75.67 +/- 3.84 mg vs. 2.33 +/- 6.14 mg, P < 0.001; axial length differences: 0.80 +/- 0.05 mm vs. 0.03 +/- 0.04 mm, P < 0.001). Oxyphenonium-treated retinas showed no damage. Of the other compounds, several elicited partial rescue and/or damaged the retina, whereas others had no effect. Oxyphenonium prevents FDM in chicks. The ineffectiveness or partial effectiveness of other compounds, coupled with the high concentrations of effective compounds required to prevent FDM, suggests that muscarinic antagonists act to prevent FDM, either at sites distant from the retina, or through a nonmuscarinic mechanism, on which only some of these drugs act.