title: Comparison of refractive development and retinal dopamine in OFF pathway mutant and C57BL/6J wild-type mice.
abstract: OBJECTIVE
  Proper visual transmission depends on the retinal ON and OFF pathways. We used Vsx1-/- mice with a retinal OFF visual pathway defect to determine the role of OFF pathway signaling in refractive development (RD) of the eye.
  
  
  METHODS
  Refractive development was measured every 2 weeks in Vsx1-/-, Vsx1+/+ (both on 129S1/Sv background), and commonly used C57BL/6J mice from 4 to 12 weeks of age. Form deprivation (FD) was induced monocularly from 4 weeks of age using head-mounted diffuser goggles. Refractive state, corneal curvature, and ocular biometry were obtained weekly using photorefraction, keratometry, and 1310 nm spectral-domain optical coherence tomography. Retinal dopamine and its metabolite, 3,4-dihydroxyphenylacetate (DOPAC), were measured using high-performance liquid chromatography (HPLC).
  
  
  RESULTS
  During normal development, the Vsx1-/- and Vsx1+/+ mice showed similar myopic refractions at younger ages (4 weeks, Vsx1-/-: -5.28±0.75 diopter (D); WT: -4.73±0.98 D) and became significantly hyperopic by 12 weeks of age (Vsx1-/-: 3.28±0.82 D; WT: 5.33±0.81 D). However, the C57BL/6J mice were relatively hyperopic at younger ages (mean refraction at 4 weeks, 3.40±0.43 D), and developed more hyperopic refractions until about 7 weeks of age (8.07±0.55 D) before stabilizing. Eight weeks of FD did not induce a myopic shift in the 129S1/Sv animals (0.16±0.85 D), as opposed to a significant shift of -4.29±0.42 D in the C57BL/6J mice. At 4 weeks of visual development, dopamine turnover (the DOPAC/dopamine ratio) was significantly greater in the 129S1/Sv mice compared to the C57BL/6J mice. FD did not alter the levels of dopamine between the goggled and opposite eyes for any genotype or strain.
  
  
  CONCLUSIONS
  OFF pathway signaling may not be critically important for normal refractive development in mice. Elevated retinal dopamine turnover in early refractive development may prevent FD myopia in 129S1/Sv mice compared to C57BL/6J mice.
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA ; Atlanta VA Center of Visual and Neurocognitive Rehabilitation, Decatur, GA.
authors.forename: Ranjay
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA ; Atlanta VA Center of Visual and Neurocognitive Rehabilitation, Decatur, GA.
authors.forename: Han na
authors.initials: Hn
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA ; Department of Neuroscience, Emory University School of Medicine, Atlanta, GA.
authors.forename: Moe H
authors.initials: MH
authors.lastname: Aung
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Tan
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA.
authors.forename: Curran S
authors.initials: CS
authors.lastname: Sidhu
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA ; Department of Neuroscience, Emory University School of Medicine, Atlanta, GA ; Department of Pharmacology, Emory University School of Medicine, Atlanta, GA.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA ; Department of Neuroscience, Emory University School of Medicine, Atlanta, GA ; Atlanta VA Center of Visual and Neurocognitive Rehabilitation, Decatur, GA.
authors.forename: Machelle T
authors.initials: MT
authors.lastname: Pardue
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics*; D006956:Hyperopia / Q000235:genetics* / Q000503:physiopathology; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012029:Refraction, Ocular; D012683:Sensory Deprivation; D041623:Tomography, Optical Coherence; D014795:Visual Pathways / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; C491582:Vsx1 protein, mouse; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine