Abstract
Purpose :
Although there is suggestive pharmacological evidence that dopamine D2 receptor activation promotes form-deprivation myopia (FDM) development, this notion requires further validation. This uncertainty exists because the drugs used for this purpose are only proved to be effective on development of FDM, but the exact cause and mechanism of myopia is unknown. To address this question, we evaluated the effects of a dopamine D2 receptor partial agonist, aripiprazole, to assess D2 receptor involvement in controlling FDM development.
Methods :
C57BL/6 mice were raised either in a visually normal environment or wore sight compromising goggles inducing FDM development from a postnatal age of 28 to 56 days. Both groups were divided into 4 sub-groups including control, vehicle and two different aripiprazole dosage (1 mg/kg and 10 mg/kg) treatments groups who were injected in the peritoneum with this drug. Their body weight, refraction, corneal radius of curvature, and ocular axial components were measured prior to and after the experiment. Monocular photopic flash electroretinograms were recorded from the form-deprived eyes.
Results :
In normal mice, daily injection of aripiprazole did not affect normal postnatal refraction development. However, in the FDM group, the higher aripiprazole dose attenuated form deprived myopia development (5.98 ± 0.92D in FDM - aripiprazole versus 10.38 ± 0.88D in FDM - vehicle, p<0.05), with a shortened vitreous chamber depth (0.015 ± 0.006mm in FDM - Aripiprazole versus 0.035 ± 0.003mm in FDM - vehicle, p<0.05). Neither of the drug treatments altered corneal radius of curvature and other axial components from those in the vehicle –treated and control groups. The aripiprazole dose did not affect FDM development at low dose, but decreased the ERG b-wave amplitudes of the form-deprived eyes in a dose-dependent manner.
Conclusions :
Aripiprazole only attenuated FDM without altering refraction development under normal vision environment or in vehicle injected mice. This dependence on form deprivation suggests that vision obstruction may somehow alter the response patterns controlled by D2R-linked signaling. Additional studies are warranted to gain insight into the underlying molecular mechanisms accounting for why aripiprazole suppresses myopia development.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.