title: Altered Refractive Development in Mice With Reduced Levels of Retinal Dopamine.
abstract: OBJECTIVE
  The neuromodulator dopamine (DA) has been implicated in the prevention of excessive ocular elongation and myopia in various animal models. This study used retina-specific DA knockout mice to investigate the role of retinal DA in refractive development and susceptibility to experimental myopia.
  
  
  METHODS
  Measurements of refractive error, corneal curvature, and ocular biometrics were obtained as a function of age for both untreated and form-deprived (FD) groups of retina-specific tyrosine hydroxylase knockout (rTHKO) and control (Ctrl) mice. Retinas from each group were analyzed by HPLC for levels of DA and its primary metabolite (DOPAC).
  
  
  RESULTS
  Under normal visual conditions, rTHKO mice showed significantly myopic refractions (F(1,188) = 7.602, P < 0.001) and steeper corneas (main effect of genotype F(1,180) = 5.1, P < 0.01) at 4 and 6 weeks of age compared with Ctrl mice. Retina-specific THKO mice also had thinner corneas (main effect of genotype F(1,181) = 37.17, P < 0.001), thinner retinas (F(6,181) = 6.07, P < 0.001), and shorter axial lengths (F(6,181) = 3.78, P < 0.01) than Ctrl mice. Retina-specific THKO retinas contained less than 15% of DA and DOPAC compared with Ctrl retinas, and the remaining DA had a significantly higher turnover, as indicated by DOPAC/DA ratios (Student's t-test, P < 0.05). Retina-specific THKO mice showed similar, yet more variable, responses to 6 weeks of FD compared with Ctrl mice.
  
  
  CONCLUSIONS
  Diminished retinal DA induced spontaneous myopia in mice raised under laboratory conditions without form deprivation. The relative myopic shift in rTHKO mice may be explained by steeper corneas, an unexpected finding. The chronic loss of DA did not significantly alter the FD myopia response in rTHKO mice.
authors.affiliation: Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States 2Biology, Emory University, Atlanta, Georgia, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bergen
authors.affiliation: Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Han Na
authors.initials: HN
authors.lastname: Park
authors.affiliation: Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States 3Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Ranjay
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States 4Neuroscience, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Erica G
authors.initials: EG
authors.lastname: Landis
authors.affiliation: Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Curran
authors.initials: C
authors.lastname: Sidhu
authors.affiliation: Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States 4Neuroscience, Emory University School of Medicine, Atlanta, Georgia, United States 5Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.affiliation: Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States 3Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States 4Neuroscience, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Machelle T
authors.initials: MT
authors.lastname: Pardue
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009216:Myopia / Q000378:metabolism* / Q000503:physiopathology; D012029:Refraction, Ocular / Q000502:physiology*; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D041623:Tomography, Optical Coherence
chemical_list: D015415:Biomarkers; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine