PURPOSE: While retinal dopamine (DA) has been long implicated in myopia development, current studies demonstrate that retinal DA levels are unaltered in C57BL/6 mice with form-deprivation myopia. This work was undertaken to explore whether and how refractive development is perturbed in this mouse strain when retinal DA levels are reduced by 6-hydroxydopamine (6-OHDA) administration.
METHODS: 6-OHDA of different doses was intravitreally applied. Retinal DA levels were measured by HPLC and TH levels analyzed by quantitative Western blotting. To choose appropriate 6-OHDA doses that significantly reduce retinal DA levels, but caused minimal disturbance of overall retinal physiology, ERG analysis was performed. Refractive errors were measured using a photorefractor, and ocular biometry assessed with optical coherence tomography and photokeratometry.
RESULTS: 6-OHDA of 6.25 μg and 12.5 μg significantly reduced retinal levels of DA and TH, but did not significantly affect ERG a- and b-wave amplitudes. With normal visual experience, 6-OHDA induced myopic refractive shifts in a dose-dependent fashion. Form-deprivation induced further myopic shifts in 6-OHDA injected eyes, but did not cause further decline in retinal DA. Furthermore, 6-OHDA administration resulted in a shorter axial length and a steeper cornea, while form-deprivation led to a longer axial length, without changing the corneal radius of curvature.
CONCLUSIONS: Reducing retinal DA levels by 6-OHDA led to myopic refractive shifts in C57BL/6 mice, which mainly resulted from a steeper cornea. We propose that, in addition to the DA-independent mechanism for form-deprivation induced myopic refractive shifts, there is a DA-dependent mechanism in parallel that underlies myopic refractive shifts in this mouse strain.