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The Role of Retinal Dopamine in C57BL/6 Mouse Refractive Development as Revealed by Intravitreal Administration of
Xiao-Hua Wu1, Kang-Wei Qian2, Guo-Zhong Xu2
1Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China 2Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Purpose:
Although 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:
On two successive days, 6-OHDA was injected into the vitreous of P18 mice. 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 cause minimal disturbance of overall retinal physiology, ERG analysis was performed. Refractive errors were measured using a photorefractor, and ocular biometry performed with optical coherence tomography and photokeratometry.
Results:
Administration of 6-OHDA of 6.25 μg and 12.5 μg significantly reduced retinal levels of DA and TH, but without affecting 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, whereas form deprivation led to a longer axial length, without changing the corneal radius of curvature.
Conclusions:
Reducing retinal DA levels led to myopic refractive shifts in C57BL/6 mice, which mainly resulted from a steeper cornea. In addition to the DA-independent mechanism for form-deprivation myopia, there is a DA-dependent mechanism in parallel that underlies myopic refractive shifts under normal laboratory conditions in this mouse strain.
