title: Visually-driven ocular growth in mice requires functional rod photoreceptors.
abstract: OBJECTIVE
  Proper refractive eye growth depends on several features of the visual image and requisite retinal pathways. In this study, we determined the contribution of rod pathways to normal refractive development and form deprivation (FD) myopia by testing Gnat1(-/-) mice, which lack functional rods due to a mutation in rod transducin-α.
  
  
  METHODS
  Refractive development was measured in Gnat1(-/-) (n = 30-36) and wild-type (WT) mice (n = 5-9) from 4 to 12 weeks of age. FD was induced monocularly from 4 weeks of age using head-mounted diffuser goggles (Gnat1(-/-), n = 9-10; WT, n = 7-8). Refractive state and ocular biometry were obtained weekly using a photorefractor, 1310 nm optical coherence tomography, and partial coherence interferometry. We measured retinal dopamine and its metabolite, DOPAC, using HPLC.
  
  
  RESULTS
  During normal development, the refractions of WT mice started at 5.36 ± 0.68 diopters (D) and became more hyperopic before plateauing at 7.78 ± 0.64 D. In contrast, refractions in Gnat1(-/-) mice were stable at 7.39 ± 1.22 D across all ages. Three weeks of FD induced a 2.54 ± 0.77 D myopic shift in WT mice, while Gnat1(-/-) mice did not respond to FD at any age. Axial lengths of Gnat1(-/-) and WT mice increased with age, but differences between genotypes or with goggling did not reach statistical significance and fell within the precision of the instruments. The DOPAC levels were significantly lower in Gnat1(-/-) mice from 2 to 12 weeks of age with DOPAC/dopamine ratio peaking earlier in Gnat1(-/-) compared to WT mice. No differences in dopamine were seen in response to FD or between genotypes.
  
  
  CONCLUSIONS
  Functional rod photoreceptors are critical to normal refractive development and the response to FD in mice. Dopamine levels may not directly modulate the refractive state of the mouse eye, but tonic levels of dopamine during development may determine susceptibility to myopia.
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Han na
authors.initials: Hn
authors.lastname: Park
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Seema B
authors.initials: SB
authors.lastname: Jabbar
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Tan
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Curran S
authors.initials: CS
authors.lastname: Sidhu
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Jane
authors.initials: J
authors.lastname: Abey
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Fazila
authors.initials: F
authors.lastname: Aseem
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Gregor
authors.initials: G
authors.lastname: Schmid
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States Atlanta Veterans Administration Center of Visual and Neurocognitive Rehabilitation, Decatur, Georgia, United States.
authors.forename: Machelle T
authors.initials: MT
authors.lastname: Pardue
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D005123:Eye / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D051379:Mice; D009216:Myopia / Q000378:metabolism / Q000473:pathology*; D012029:Refraction, Ocular; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D041623:Tomography, Optical Coherence; D015293:Transducin / Q000096:biosynthesis*
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D015293:Transducin; D004298:Dopamine
keywords: dopamine; myopia; refractive development; rod photoreceptors