The M1 Muscarinic Antagonist Pirenzepine Reduces Myopia and Eye Enlargement in the Tree Shrew

Invest Ophthalmol Vis Sci. 1996 Jun;37(7):1368-79.

Abstract

Purpose: To determine the efficacy of the M1-selective muscarinic antagonist, pirenzepine, in preventing experimentally induced myopia in a mammalian model, the tree shrew.

Methods: Tree shrews were monocularly deprived (MD) using translucent goggles or negative lenses for a period of 12 days. In two of the MD groups, tree shrews received daily subconjunctival administration of either pirenzepine (17.7 mumol; n = 9) or vehicle control (n = 6). Control groups (n = 6) were used to assess the effects of MD, injection regimen, and drug effects.

Results: In sham-injected and saline-injected MD tree shrews, 12 days of MD produced-13.2 D +/- 0.8 D and -14.1 D +/- 0.5 D of axial myopia, respectively. In pirenzepine-injected MD tree shrews, 12 days of MD induced an axial myopia of only -2.1 D +/- 1.4 D. The significant reduction in myopia in pirenzepine-injected MD tree shrews was caused by significantly less vitreous chamber elongation of the deprived eye (0.05 mm +/- 0.04 mm) relative to the contralateral control eye when compared to sham-injected and saline-injected MD tree shrews (0.24 mm +/- 0.02 mm and 0.29 mm +/- 0.01 mm). Mean equatorial enlargement and increased eye weight were prevented in pirenzepine-injected MD tree shrews (P < 0.01). Pirenzepine also was found to reduce myopia and ocular enlargement in lens defocus-induced myopia. Control experiments demonstrated that pirenzepine did not cause a significant reduction in amplitude of carbachol-induced accommodation.

Conclusions: Findings demonstrate that chronic administration of the M1-selective muscarinic antagonist, pirenzepine, prevents experimentally induced myopia in this mammalian model by a nonaccommodative mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Accommodation, Ocular
  • Animals
  • Conjunctiva
  • Disease Models, Animal
  • Eye / drug effects
  • Eye / pathology*
  • Hypertrophy / etiology
  • Hypertrophy / pathology
  • Hypertrophy / prevention & control
  • Injections
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / therapeutic use*
  • Myopia / etiology
  • Myopia / pathology
  • Myopia / prevention & control*
  • Pirenzepine / administration & dosage
  • Pirenzepine / therapeutic use*
  • Refraction, Ocular
  • Retina / drug effects
  • Retina / pathology
  • Sclera / drug effects
  • Sclera / pathology
  • Sensory Deprivation
  • Tupaiidae

Substances

  • Muscarinic Antagonists
  • Pirenzepine