ON pathway mutations increase susceptibility to form-deprivation myopia

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±33.0pg/mg) compared to their WT counterparts (197.5±11.2pg/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.