title: The Role of Retinal Dopamine in C57BL/6 Mouse Refractive Development as Revealed by Intravitreal Administration of 6-Hydroxydopamine.
abstract: OBJECTIVE
  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.
authors.affiliation: Institutes 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.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Wu
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Kang-Wei
authors.initials: KW
authors.lastname: Qian
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Xu
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Yun-Yun
authors.initials: YY
authors.lastname: Li
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ma
authors.affiliation: School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Furong
authors.initials: F
authors.lastname: Huang
authors.affiliation: Institutes 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.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiangtian
authors.initials: X
authors.lastname: Zhou
authors.affiliation: School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Xiong-Li
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhong
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Weng
mesh_terms: D018663:Adrenergic Agents / Q000008:administration & dosage; D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography; D005500:Follow-Up Studies; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009216:Myopia / Q000175:diagnosis / Q000378:metabolism*; D016627:Oxidopamine / Q000008:administration & dosage*; D012029:Refraction, Ocular; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D041623:Tomography, Optical Coherence / Q000379:methods*
chemical_list: D018663:Adrenergic Agents; D016627:Oxidopamine; D004298:Dopamine