Daily Injection But Not Continuous Infusion of Apomorphine Inhibits Form-Deprivation Myopia in Mice

Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2475-85. doi: 10.1167/iovs.13-12361.

Abstract

Purpose: To compare the effects of daily injection versus continuous infusion of a nonspecific dopamine agonist, apomorphine (APO), on refraction and ocular growth in normal postnatal mice and mice with form-deprivation myopia (FDM).

Methods: The C57BL/6 mice were subjected (or not) to monocular FD by covering the left eye with a frosted goggle and leaving the right (fellow) eye uncovered. During postnatal days 28 to 56, both groups received APO (5 mg/kg/d) or vehicle either as daily intraperitoneal injection or by continuous subcutaneous infusion with mini-pumps. After these treatments, binocular refractions were measured by photoretinoscopy and binocular ocular dimensions were measured by optical coherence tomography. Monocular photopic flash electroretinograms were recorded from non-FD mice.

Results: In normal mice, daily injection or continuous infusion of APO did not affect normal postnatal development of refraction. However, in the FD group, daily APO-injection attenuated ocular growth and also myopia development, as reflected in the interocular differences for APO-injected mice compared with vehicle-injected mice: (1) refraction, -1.04 ± 0.37 diopter (D) (APO-injection) compared with -4.14 ± 0.77 D (vehicle-injection) (P < 0.05); (2) vitreous chamber depth: -0.002 ± 0.005 mm compared with 0.032 ± 0.009 mm (P < 0.05); and (3) axial length: 0.000 ± 0.005 mm compared with 0.057 ± 0.007 mm (P < 0.05). By contrast, continuous APO-infusion failed to affect these biometric parameters. Furthermore, daily APO-injection decreased the ERG a- and b-wave amplitudes, whereas continuous APO-infusion increased these responses.

Conclusions: In monocularly FD mice, daily APO-injection, but not continuous infusion, attenuated myopia development. Therefore, evaluating different dopamine agonist administration paradigms is important for identifying effective dopamine-based treatment for myopia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / administration & dosage*
  • Disease Models, Animal
  • Dopamine Agonists / administration & dosage
  • Drug Administration Schedule
  • Infusions, Parenteral
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myopia / drug therapy*
  • Myopia / etiology
  • Myopia / physiopathology
  • Refraction, Ocular*
  • Sensory Deprivation

Substances

  • Dopamine Agonists
  • Apomorphine