26 research outputs found

    Analysis of Postnatal Eye Development in the Mouse with High-Resolution Small Animal Magnetic Resonance Imaging

    Get PDF
    PURPOSE. Studies of myopia in mice have been complicated by the difficulty in obtaining accurate measurements of small changes observed in the growing mouse eye in vivo and the lack of data on refractive eye development. The purpose of this study was to carry out an in vivo high-resolution analysis of mouse eye growth and refractive development. METHODS. High-resolution small animal magnetic resonance imaging and high-resolution infrared photorefraction were used to analyze refractive development in postnatal day (P)21 to P89 C57BL/6J mice. RESULTS. The growth of the mouse eye decelerated after P40. The eye maintained a slightly prolate shape during growth. The anterior chamber growth exhibited a similar pattern, whereas the corneal radius of curvature (CRC) increased linearly. The growth rate of the lens remained constant until P89. The lens "overgrew" the eye at P40, resulting in a decline in vitreous chamber depth. Mice showed myopic refractive errors at a younger age (Ϫ13.2 Ϯ 2.0 D; mean Ϯ SD, P21). The refractive errors stabilized around emmetropic values by P32 and remained emmetropic until P40. Mice became progressively hyperopic with age (ϩ1.2 Ϯ 1.7 D, P67; ϩ3.6 Ϯ 2.3 D, P89). CONCLUSIONS. Development of ocular components in the mouse is similar to that of the tree shrew but different from that of higher primates and humans. Primary differences can be attributed to the age-related changes of the crystalline lens and CRC. In spite of these differences, mice appear to be able to achieve and maintain emmetropic refractive status at P32 to P40. (Invest Ophthalmol Vis Sci. 2010;51:21-27) DOI:10.1167/iovs.08-2767 P ostnatal eye development is a tightly coordinated process whereby visual input regulates growth of the eye in a process called emmetropization. 1 Emmetropization is a result of the eye's capacity to adjust its growth during early postnatal development according to the quality of the image received by the retina. In the emmetropic primate eye, the refractive power of the optical media is tightly linked to the size of its vitreous chamber. 2,3 The failure of emmetropization often leads to the development of myopia. Approximately 20% to 30% of the myopic population has high myopia, which is often accompanied by serious complications such as retinal detachment and posterior staphyloma. 4 Degradation of the visual input by eyelid fusion, diffusers, or spectacle lenses during the early postnatal period has been shown to lead to the abnormal enlargement of the eye and the development of myopia in several vertebrate species, including nonhuman primates, 8 tree shrews, 9 and chickens. 11 This, combined with a number of wellestablished techniques for genome manipulation, has made it a very popular model for studies of visual system plasticity, 14,22-27 For the same reasons, the mouse may become a very powerful tool in studies of refractive eye development and myopia. Several recent cross-sectional studies of postnatal mouse eye development have established the general pattern of postnatal mouse eye growth. 28 -32 One study using optical low coherence interferometry (OLCI) measurements of the axial length suggested that the mouse eye stops growing at around postnatal day (P)40. In the present study, we used high-resolution small animal magnetic resonance imaging (MRI) and high-resolution automated eccentric infrared photorefractometry to conduct a longitudinal study of the normal development of the refractive state and the dimensions of ocular components in C57BL/6J mice. We show that different eye components exhibit unique growth patterns during early postnatal development. We also show that, similar to other mammals, mice undergo emmetropization after birth. These results make the mouse a highly useful species for studies in refractive eye development and myopia

    APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans

    Get PDF
    Myopia is the most common vision disorder and the leading cause of visual impairment worldwide. However, gene variants identified to date explain less than 10% of the variance in refractive error, leaving the majority of heritability unexplained (“missing heritability”). Previously, we reported that expression of APLP2 was strongly associated with myopia in a primate model. Here, we found that low-frequency variants near the 5’-end of APLP2 were associated with refractive error in a prospective UK birth cohort (n = 3,819 children; top SNP rs188663068, p = 5.0 × 10−4) and a CREAM consortium panel (n = 45,756 adults; top SNP rs7127037, p = 6.6 × 10−3). These variants showed evidence of differential effect on childhood longitudinal refractive error trajectories depending on time spent reading (gene x time spent reading x age interaction, p = 4.0 × 10−3). Furthermore, Aplp2 knockout mice developed high degrees of hyperopia (+11.5 ± 2.2 D, p −4) compared to both heterozygous (-0.8 ± 2.0 D, p −4) and wild-type (+0.3 ± 2.2 D, p −4) littermates and exhibited a dose-dependent reduction in susceptibility to environmentally induced myopia (F(2, 33) = 191.0, p −4). This phenotype was associated with reduced contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10−4) and changes in the electrophysiological properties of retinal amacrine cells, which expressed Aplp2. This work identifies APLP2 as one of the “missing” myopia genes, demonstrating the importance of a low-frequency gene variant in the development of human myopia. It also demonstrates an important role for APLP2 in refractive development in mice and humans, suggesting a high lev

    Mouse Experimental Myopia Has Features of Primate Myopia

    No full text
    High-resolution MRI analysis of mouse experimental myopia revealed that the development of myopia in mice is attributed to axial elongation of the vitreous chamber of the eye, as in humans and nonhuman primates
    corecore