Wnt/β-catenin 通路对形觉剥夺小鼠巩膜重塑的影响。

The effect of Wnt/β-catenin pathway on the scleral remolding in the mouse during form deprivation.

机构信息

Department of Ophthalmology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Int Ophthalmol. 2021 Sep;41(9):3099-3107. doi: 10.1007/s10792-021-01875-1. Epub 2021 May 13.

DOI:10.1007/s10792-021-01875-1

PMID:33983548

Abstract

BACKGROUND

Many reports have shown that Wnt/β-Catenin pathway is associated with a variety of diseases, but its role in the pathogenesis of myopia is still unknown. In order to clarify the role of Wnt/β-catenin pathway in the development of form deprivation myopia (FDM), this study investigated the expression of scleral Wls, β-catenin and TCF4 in mice model of form deprivation (FD) myopia.

METHODS

Three parallel experimental groups, including FD, monocular exposure (SC) and binocular exposure (NC) group, were designed to investigate the effects of Wnt/β-Catenin pathway on scleral remodeling mouse during form deprivation in three-week-old C57BL/6 mice. Diopters and axial lengths (AL) in each sample were measured with an infrared eccentric refractometer or spectral-domain optical coherence tomography. The expression of scleral Wls, β-catenin and TCF4 were detected with Western blot. Morphological changes of posterior sclera were observed with a transmission electron microscope (TEM). The above characterization and analysis were performed on the 0th, 7th, 14th, 21st and 28th days, respectively.

RESULTS

The difference of diopter and AL between the three groups (SC, NC and FD group) gradually increased with the prolongation of FD time (except AL between SC and NC groups). The changes of diopter and AL gradually increased with the prolongation of FD time. Especially, the diopter and AL will increase sharply after FD lasts for a long time, such as the measurement on the 21st for diopter and 28th days for AL. Most notably, the AL of FD eyes significantly increased after 28 days of deprivation. Thinning and disordered arrangement of collagen fibers and a decrease of extracellular matrix were observed with TEM. The expression of scleral Wls, β-catenin and TCF4 increased with age in the NC and SC group. In FD group, they increased significantly on the 7th, 14th and 21st days but decreased on the 28th day.

CONCLUSIONS

The expression of Wls, β-Catenin and TCF4 to FD were more sensitive indicators than that of diopter and AL. Within the first 7 days of FD, the expression of Wls, β-Catenin and TCF4 in sclera increased sharply. With the extension of FD duration, it gradually decreased. It is suggested that the Wnt/β-catenin pathway might be involved in the scleral remodeling induced in FDM mice.

摘要

背景

许多报道表明 Wnt/β-连环蛋白通路与多种疾病有关，但它在近视发病机制中的作用尚不清楚。为了阐明 Wnt/β-连环蛋白通路在形觉剥夺性近视（FDM）发展中的作用，本研究探讨了 Wnt/β-连环蛋白通路在形觉剥夺性近视小鼠模型中的巩膜 Wls、β-连环蛋白和 TCF4 的表达。

方法

设计了 3 个平行实验组，包括形觉剥夺（FD）、单眼暴露（SC）和双眼暴露（NC）组，以研究 Wnt/β-连环蛋白通路对 3 周龄 C57BL/6 小鼠形觉剥夺时巩膜重塑的影响。用红外偏心折射计或谱域光相干断层扫描仪测量每个样本的屈光度和眼轴长度（AL）。用 Western blot 检测巩膜 Wls、β-连环蛋白和 TCF4 的表达。用透射电镜（TEM）观察后巩膜的形态变化。以上特征和分析分别在第 0、7、14、21 和 28 天进行。

结果

3 组（SC、NC 和 FD 组）之间的屈光度和 AL 差异随着 FD 时间的延长而逐渐增大（SC 组和 NC 组之间的 AL 差异除外）。随着 FD 时间的延长，屈光度和 AL 的变化逐渐增大。特别是 FD 后长时间，如第 21 天的屈光度和第 28 天的 AL 测量值会急剧增加。最值得注意的是，FD 眼的 AL 在 28 天后明显增加。TEM 观察到胶原纤维变薄、排列紊乱，细胞外基质减少。NC 和 SC 组中巩膜 Wls、β-连环蛋白和 TCF4 的表达随年龄增长而增加。在 FD 组中，它们在第 7、14 和 21 天显著增加，但在第 28 天减少。