Contributions of Dopamine D4 Receptor Modulation to the Development of Normal Refraction and Form-Deprivation Myopia in Mice

Objective: To investigate the role of dopamine D4 receptor (D4R) in the development of normal refraction and form-deprivation myopia (FDM) by applying D4R agonist PD-168077 and D4R antagonist L-745870 in mice. Methods: This was an animal experimental study. Four-week-old C57BL/6 mice were raised either in a visually normal environment or subjected to FDM by covering one eye with vision obstructing goggles while the other eye served as the normal control. Both groups were divided into sub-groups including vehicle and drug groups (D4R agonist PD-168077: 1 mg/kg/day and 10 mg/kg/day; D4R antagonist L-745870: 1 mg/kg/day and 10 mg/kg/day). They were intraperitoneally injected daily for two weeks. ERG was measured in normal enviroment mice on postnatal day 35. Refraction, corneal curvature radius, and ocular axial components were measured in all animals prior to and after each experiment. Statistical analyses were performed by a paired t test, one-way ANOVA, and repeated measurement ANOVA. Results: Normal refractive development was not affected by D4R agonist PD-168077 treatment. On the other hand, the D4R antagonist L-745870 enhanced normal refractive development towards hyperopia at a dose of 10 mg/kg (P=0.047) with no significant changes in other biometric parameters. PD-168077 increased the ERG OPs amplitude under scotopic conditions at an intensity of -0.699 log cdsm-2 (P=0.04), while L-745870 had no significant effect on the a-wave, b-wave, or summed OPs amplitudes under scotopic and photopic conditions. The development of FDM was promoted by PD-168077 treatment (P=0.004), with increases in both vitreous chamber depth and axial length. In contrast, D4R antagonist L-745870, inhibited FDM (P<0.001), with a shortened vitreous chamber depth and axial length. No significant changes in anterior chamber depth, lens thickness or corneal curvature radius were observed. Conclusions: D4R is activated or inactivated had no significant effects on normal refractive development in mice. In contrast, in a form-deprived environment, D4R is activated enhance while D4R inactivated inhibit FDM development, suggesting D4R activation enhances while D4R inactivation inhibits the development of myopia in mice. Key words: dopamine; form-deprivation myopia; D4 receptor; mice