Wnt signaling in form deprivation myopia of the mice retina.

Wnt signaling in form deprivation myopia of the mice retina.
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小鼠视网膜形式剥夺性近视中的 Wnt 信号传导

DOI:
10.1371/journal.pone.0091086
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Ke B
Ke B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ma M;Zhang Z;Du E;Zheng W;Gu Q;Xu X;Ke B

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典型的Wnt信号通路在视网膜细胞增殖分化、轴突生长、细胞维持等过程中发挥重要作用。在此,我们在小鼠形态剥夺性近视模型中验证了Wnt信号通路的元件参与调节眼睛生长和预防近视的假设。(1)将125只C57BL/6小鼠随机分为形体剥夺性近视组和对照组。通过缝合右眼睑诱导形态剥夺性近视(FDM),对照组不进行任何治疗。治疗1、2和4周后,通过睫状体瘫痪视网膜镜屈光和摄影或a -扫描超声测量眼轴长度在体内进行评估。RT-PCR和western blotting分别检测各组大鼠视网膜Wnt2b、Fzd5和β-catenin mRNA和蛋白水平。(2)将96只小鼠分为对照组、纯药物组和药物+FDM组(通过扩散器)。实验治疗后两组的眼睛接受玻璃体内注射或蛋白,DKK-1 (wnt通路拮抗剂)或Norrin (wnt通路激动剂),每三天一次,共注射4次。在失形后第14天测定眼轴长和视镜屈光度。在形态剥夺1、2和4周后,与对侧眼相比,FDM眼有相对近视的屈光不正。对照组左、右眼屈光不正无显著性差异。无形态近视眼Wnt2b、Fzd5和β-catenin mRNA和蛋白的表达量显著高于对照组。DKK-1(拮抗剂)减少屈光不正的近视位移和增加轴向伸长,而Norrin在FDM眼睛中具有相反的作用。本研究首次证明Wnt2b信号通路可能在哺乳动物模型中形式剥夺性近视的发生和发展中发挥作用。
Background The canonical Wnt signaling pathway plays important roles in cellular proliferation and differentiation, axonal outgrowth, cellular maintenance in retinas. Here we test the hypothesis that elements of the Wnt signaling pathway are involved in the regulation of eye growth and prevention of myopia, in the mouse form-deprivation myopia model. Methodology/Principal Findings (1) One hundred twenty-five C57BL/6 mice were randomly distributed into form-deprivation myopia and control groups. Form-deprivation myopia (FDM) was induced by suturing the right eyelid, while the control group received no treatment. After 1, 2, and 4 weeks of treatment, eyes were assessed in vivo by cycloplegic retinoscopic refraction and axial length measurement by photography or A-scan ultrasonography. Levels of retinal Wnt2b, Fzd5 and β-catenin mRNA and protein were evaluated using RT-PCR and western blotting, respectively. (2) Another 96 mice were divided into three groups: control, drugs-only, and drugs+FDM (by diffuser). Experimentally treated eyes in the last two groups received intravitreal injections of vehicle or the proteins, DKK-1 (Wnt-pathway antagonist) or Norrin (Wnt-pathway agonist), once every three days, for 4 injections total. Axial length and retinoscopic refraction were measured on the 14th day of form deprivation. Following form-deprivation for 1, 2, and 4 weeks, FDM eyes had a relatively myopic refractive error, compared with contralateral eyes. There were no significant differences in refractive error between right and left eye in control group. The amounts of Wnt2b, Fzd5 and β-catenin mRNA and protein were significantly greater in form-deprived myopia eyes than in control eyes.DKK-1 (antagonist) reduced the myopic shift in refractive error and increase in axial elongation, whereas Norrin had the opposite effect in FDM eyes. Conclusions/Significance Our studies provide the first evidence that the Wnt2b signaling pathway may play a role in the development and progression of form-deprivation myopia, in a mammalian model.
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发表时间: 2010-07-09
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