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Andrei V. Tkatchenko, Yimin Shen, Tatiana V. Tkatchenko; Genetic Background Modulates Refractive Eye Development And Susceptibility To Myopia In The Mouse. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3465.
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Refractive eye development is controlled by both environmental and genetic factors. However, contribution of genetic factors accounts for at least 80% of variance in refraction in humans. The purpose of this study was to determine whether genetic background influences refractive eye development and susceptibility to experimental myopia in mice.
Using a high-resolution automated eccentric infrared photorefractor and high-resolution MRI, normal refractive eye development and susceptibility to experimental myopia was compared in three genetically distant mouse strains, i.e., C57BL/6J, C57L/J and CZECHII/EiJ.
First, we have measured age-related changes in refraction in all three strains. We confirmed our previous observation that C57BL/6J mice are born myopic and then undergo emmetropization, achieving adult-level emmetropia (zero refractive error) at P32 (P21, -13.2 ± 2.0; P32, -0.5 ± 1.5; P40, +0.3 ± 0.9; P67, +1.2 ± 1.7; P89, +3.6 ± 2.3). C57L/J mice were also born myopic; however, unlike C57BL/6J mice, C57L/J mice did not undergo emmetropization and remained myopic throughout adulthood (P21, -13.9 ± 3.2; P32, -13.1 ± 2.7; P40, -13.0 ± 2.7; P67, -9.9 ± 2.1; P89, -9.9 ± 2.5). CZECHII/EiJ mice were born hyperopic and remained hyperopic throughout adulthood (P21, +31.9 ± 5.2; P32, +34.1 ± 5.3; P40, +36.1 ± 3.9; P67, +35.2 ± 4.0; P89, +33.0 ± 2.0). Analysis of variance (ANOVA) has revealed that refractive eye development in C57BL/6J mice was significantly different from both C57L/J (F(4,100) = 42.675, P < 0.0001) and CZECHII/EiJ mice (F(4, 96) = 21.856, P < 0.0001). We have also analyzed susceptibility to form-deprivation myopia in all three mouse strains. The largest myopic shift in refraction in the deprived eyes (compared to the control eyes) was induced in C57BL/6J mice (-12.0 ± 1.4, P < 0.0001). The smallest myopic shift in refraction was observed in CZECHII/EiJ mice (-3.8 ± 1.6, P = 0.0224), whereas C57L/J mice exhibited intermediate susceptibility to experimental myopia (-6.3 ± 2.4, P = 0.0212). Susceptibility to experimental myopia in C57BL/6J mice was significantly greater compared to both C57L/J (P = 0.002) and CZECHII/EiJ mice (P < 0.0001). High-resolution MRI also revealed significant differences in the dimensions of ocular components between the three strains.
Thus, genetic background modulates refractive eye development and susceptibility to experimental myopia in mice. We have identified three genetically distant mouse strains with strikingly different refractive eye development and significantly different susceptibility to experimentally induced myopia.
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