title: ON pathway mutations increase susceptibility to form-deprivation myopia.
abstract: The ON pathway mutation in nob mice is associated with altered refractive development, and an increased susceptibility to form-deprivation (FD) myopia. In this study, we used mGluR6-/- mice, another ON pathway mutant, to determine whether the nob phenotype was due to the Nyx mutation or abnormal ON pathway transmission. Refractive development under a normal visual environment for mGluR6-/- and age-matched wild-type (WT) mice was measured every 2 weeks from 4 to 16 weeks of age. The response to monocular FD from 4 weeks of age was measured weekly in a separate cohort of mice. Refraction and ocular biometry were obtained using a photorefractor and optical coherence tomography. Retinas were harvested at 16 weeks, and analyzed for dopamine (DA) and DOPAC using high-performance liquid chromatography. Under normal conditions, mGluR6-/- mice were significantly more myopic than their WT controls (refraction at 12 weeks; WT: 9.40 ± 0.16 D, mGluR6-/-: 6.91 ± 0.38 D). Similar to nob mice, two weeks of FD resulted in a significant myopic shift of -5.57 ± 0.72 D in mGluR6-/- mice compared to -1.66 ± 0.19 D in WT animals. No significant axial length changes were observed with either normal or FD visual conditions. At 16 weeks, mGluR6-/- retinas showed significantly lower DOPAC levels (111.2 ± 33.0 pg/mg) compared to their WT counterparts (197.5 ± 11.2 pg/mg). Retinal DA levels were similar between the different genotypes. Our results indicate that reduced retinal DA metabolism/turnover may be associated with increased susceptibility to myopia in mice with ON pathway defect mutations.
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, USA.
authors.forename: Ranjay
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, USA.
authors.forename: Han Na
authors.initials: HN
authors.lastname: Park
authors.affiliation: Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Hanif
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Curran S
authors.initials: CS
authors.lastname: Sidhu
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA; Department of Pharmacology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: P Michael
authors.initials: PM
authors.lastname: Iuvone
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, USA; Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, USA. Electronic address: mpardue@emory.edu.
authors.forename: Machelle T
authors.initials: MT
authors.lastname: Pardue
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009216:Myopia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism; D012029:Refraction, Ocular / Q000502:physiology*; D041623:Tomography, Optical Coherence
chemical_list: D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6; D004247:DNA
keywords: Dopamine; Form-deprivation; Metabotropic glutamate receptor; Myopia; ON pathway; Refractive error