The Role of the Dopamine D2 Receptor in Form-Deprivation Myopia in Mice: Studies With Full and Partial D2 Receptor Agonists and Knockouts

Purpose: The purpose of this study was to explore the role and mechanism of D2 receptor (D2R) involvement in myopia development and the effects of the full D2R agonist quinpirole and partial D2R agonist aripiprazole on postnatal refractive development and form-deprivation myopia (FDM). Methods: C57BL/6 ("B6") mice, raised either in a visually normal or unilateral form-deprivation environment, were divided into three subgroups, including an intraperitoneally injected (IP) vehicle group and two quinpirole (1 and 10 µg/g body weight) treatment groups. The effects of quinpirole on FDM were further verified in D2R-knockout (KO) mice and corresponding wild-type littermates. Then, the modulation of normal vision development and FDM by aripiprazole (1 and 10 µg/g body weight, IP) was assessed in C57BL/6 mice. All biometric parameters were measured before and after treatments, and retinal cyclic adenosine phosphate (cAMP) and phosphorylated ERK (pERK) levels were analyzed to assess D2R-mediated signal transduction. Results: Neither quinpirole nor aripiprazole affected normal refractive development. FDM development was inhibited by quinpirole at low dose but enhanced at high dose, and these bidirectional effects were validated by D2R-specificity. FDM development was attenuated by the partial D2R agonist aripiprazole, at high dose but not at low dose. Quinpirole caused a dose-dependent reduction in cAMP levels, but had no effect on pERK. Aripiprazole reduced cAMP levels at both doses, but caused a dose-dependent increase of pERK in the form-deprived eyes. Conclusions: Reduction of D2R-mediated signaling contributes to myopia development, which can be selectively attenuated by partial D2R agonists that activate D2Rs under the low dopamine levels that occur with FDM.