充足的胆碱供应,一种必需的营养素,是必要的,以支持适当的大脑发育。目前尚不清楚产前胆碱的可用性是否在视觉系统发育中起作用。在这项研究中,我们讨论了子宫内胆碱供应对小鼠模型视网膜发育和后期功能的作用。我们在怀孕期间降低了母体饮食中的胆碱可用性,并评估了发育中的产前视网膜中视网膜祖细胞(RPCs)的增殖和分化特性,以及成年后代的视觉功能。我们报告说,在视网膜形成过程中胆碱的低可用性导致持续的视网膜细胞结构缺陷,范围从视网膜神经元移位到视网膜下间隙的局灶性病变到光感受器组织中严重的细胞不足和超微结构缺陷。我们进一步表明,低胆碱可用性损害视网膜神经元细胞的及时分化,这样早期出生的视网膜神经节细胞的密度,无长碱和水平细胞,以及圆锥感光器前体,在低胆碱胚胎d17.5视网膜中减少。维持较高比例的不能退出细胞周期的RPC是低胆碱胚胎中异常神经元分化的基础。增加RPC细胞周期长度,以及神经纤维蛋白2/Merlin蛋白的相关减少,Hippo信号通路的上游调节因子,至少在某种程度上,解释低胆碱视网膜中的异常神经发生。此外,我们发现子宫内暴露于低胆碱饮食的动物表现出显著程度的个体差异,特征在于个体动物的2只眼睛之间的明显功能差异。一起,我们的发现表明,第一次,胆碱的可用性在调节视网膜生成的时间进程中起着至关重要的作用,并为充足的胆碱供应对视觉系统正常发育的重要性提供了证据。-特鲁希略-冈萨雷斯,I.,星期五,W.B.,芒森,C.A.,Bachleda,A.,Weiss,E、R、Alam,N.M.,沙,W、Zeisel,S、H、Surzenko,N.子宫内胆碱的低可用性破坏视网膜的发育和功能。
Adequate supply of choline, an essential nutrient, is necessary to support proper brain development. Whether prenatal choline availability plays a role in development of the visual system is currently unknown. In this study, we addressed the role of in utero choline supply for the development and later function of the retina in a mouse model. We lowered choline availability in the maternal diet during pregnancy and assessed proliferative and differentiation properties of retinal progenitor cells (RPCs) in the developing prenatal retina, as well as visual function in adult offspring. We report that low choline availability during retinogenesis leads to persistent retinal cytoarchitectural defects, ranging from focal lesions with displacement of retinal neurons into subretinal space to severe hypocellularity and ultrastructural defects in photoreceptor organization. We further show that low choline availability impairs timely differentiation of retinal neuronal cells, such that the densities of early-born retinal ganglion cells, amacrine and horizontal cells, as well as cone photoreceptor precursors, are reduced in low choline embryonic d 17.5 retinas. Maintenance of higher proportions of RPCs that fail to exit the cell cycle underlies aberrant neuronal differentiation in low choline embryos. Increased RPC cell cycle length, and associated reduction in neurofibromin 2/Merlin protein, an upstream regulator of the Hippo signaling pathway, at least in part, explain aberrant neurogenesis in low choline retinas. Furthermore, we find that animals exposed to low choline diet in utero exhibit a significant degree of intraindividual variation in vision, characterized by marked functional discrepancy between the 2 eyes in individual animals. Together, our findings demonstrate, for the first time, that choline availability plays an essential role in the regulation of temporal progression of retinogenesis and provide evidence for the importance of adequate supply of choline for proper development of the visual system.-Trujillo-Gonzalez, I., Friday, W. B., Munson, C. A., Bachleda, A., Weiss, E. R., Alam, N. M., Sha, W., Zeisel, S. H., Surzenko, N. Low availability of choline in utero disrupts development and function of the retina.