Inhibition of experimental myopia by a dopamine agonist: different effectiveness between form deprivation and hyperopic defocus in guinea pigs

Abstract

Purpose: The dopamine (DA) system in the retina is critical to normal visual development as lack of retinal DA signaling may contribute to myopic development. The involvement of DA in myopic development is complex and may be different between form deprivation and hyperopic defocus. This study evaluated effects of a non-selective DA receptor agonist, apomorphine (APO) on refractive development in guinea pigs treated with form deprivation or hyperopic defocus.

Methods: APO was subconjunctivally injected daily for 11 days in form-deprived (0.025 to 2.5 ng/µl) and defocused (0.025 to 250 ng/µl) eyes. Changes in ocular biometry and retinal concentration of DA and its metabolites (DOPAC) were measured in the 2 animal models to assess the level of DA involvement in each of the models (the less the change, the lower the involvement).

Results: Similar myopic degree was induced in both the deprived and defocused eyes (-4.06 D versus -3.64 D) at 11 days of the experiment. DA and DOPAC levels were reduced in the deprived eyes but did not change significantly in the defocused eyes compared to the fellow and normal control eyes. A subconjunctival injection of APO daily for 11 days at concentrations ranged from 0.025 to 2.5 ng/µl inhibited form deprivation myopia in a concentration-dependent manner. By contrast, the APO treatment ranged from 0.025 to 250 ng/µl did not effectively inhibit the defocus-induced myopia and the associated axial elongation.

Conclusions: DA signaling may play a more critical role in form deprivation myopia than in defocus-induced myopia, raising a question whether the mechanisms of DA signaling are different under these two types of experimental myopia.

Figure 1

Retinal DA and DOPAC levels and the DOPAC/DA ratio in normal control, FDM-only and defocus-only groups. DA and DOPAC concentrations were determined in retinal extracts at day 11 of treatment (FDM: deprived eyes; FDM fel: fellow eyes to deprived eyes; defocus: defocused eyes; defocus fel: fellow eyes to defocused eyes). The levels of retinal DA, DOPAC, and the DOPAC/DA ratio were significantly lower in the deprived eyes compared to their fellow eyes (* p<0.05, paired sample t-test). The levels of DA and DOPAC in the deprived eyes were significantly lower than in the normal control eyes (*p<0.05, one-way ANOVA). In contrast, the defocus-only group showed similar levels of DA and its metabolites between eyes of the individual animals (p>0.05, one-way ANOVA). However, the defocused eyes showed a significant reduction in retinal DOPAC level but no significant changes in DA or DOPAC/DA levels when compared to the normal control eyes (*p<0.05, one-way ANOVA).

Figure 2

Time course of changes in total amount of APO in the vitreous chamber after subconjunctival injection of APO. The amount of APO in the vitreous chamber peaked 0.5 h or less after injection and decreased rapidly, reaching a plateau at 12 h and maintaining plateau levels at 24 h. The data at each time point was from cross-section measurements.

Figure 3

Biometric measurements in FDM, vehicle-FDM, and APO-FDM (0.025 to 250 ng/μl) groups before and at 11 days of FDM. A: Refraction; B: Vitreous length; C: Axial length. APO effectively blocked the development of FDM by inhibiting the excessive elongation of vitreous chamber in a dose-dependent pattern (* indicates a p<0.05 compared to the fellow eye, paired t-test).

Figure 4

Biometric measurements in defocus-only, vehicle-defocus, and APO-defocus (0.025 to 250 ng/μl) groups before and at 11 days of hyperopic defocus. A: Refraction; B: Vitreous length; C: Axial length. At the concentrations examined, APO has no statistically significant effect on the development of defocus-induced myopia.