Vision Science Program and School of Optometry, University of California, Berkeley, 693 Minor Hall, Berkeley, CA, 94720-2020, USA.
Tsinghua-Berkeley Shenzhen Institute (TBSI), UC Berkeley, Berkeley, CA, USA.
Sci Rep. 2021 Aug 31;11(1):17401. doi: 10.1038/s41598-021-96867-7.
Cataracts, named for pathological light scattering in the lens, are known to be associated with increased large protein aggregates, disrupted protein phase separation, and/or osmotic imbalances in lens cells. We have applied synchrotron phase contrast X-ray micro-computed tomography to directly examine an age-related nuclear cataract model in Cx46 knockout (Cx46KO) mice. High-resolution 3D X-ray tomographic images reveal amorphous spots and strip-like dense matter precipitates in lens cores of all examined Cx46KO mice at different ages. The precipitates are predominantly accumulated in the anterior suture regions of lens cores, and they become longer and dense as mice age. Alizarin red staining data confirms the presence of calcium precipitates in lens cores of all Cx46KO mice. This study indicates that the spatial and temporal calcium precipitation is an age-related event associated with age-related nuclear cataract formation in Cx46KO mice, and further suggests that the loss of Cx46 promotes calcium precipitates in the lens core, which is a new mechanism that likely contributes to the pathological light scattering in this age-related cataract model.
白内障，因其在晶状体中的病理性光散射而得名，已知与大蛋白聚集体的增加、蛋白质相分离的破坏以及/或晶状体细胞的渗透失衡有关。我们已经应用同步辐射相衬 X 射线微计算机断层扫描技术，直接研究 Cx46 敲除（Cx46KO）小鼠的年龄相关性核白内障模型。高分辨率 3D X 射线断层扫描图像显示，在不同年龄的所有 Cx46KO 小鼠的晶状体核中，都有不规则的点状和条状密集物质沉淀物。沉淀物主要在前晶状体缝线区域积累，随着小鼠年龄的增长，它们变得更长、更密集。茜素红染色数据证实了所有 Cx46KO 小鼠晶状体核中钙沉淀物的存在。本研究表明，空间和时间上的钙沉淀是与 Cx46KO 小鼠年龄相关性核白内障形成相关的年龄相关事件，并进一步表明 Cx46 的缺失促进了晶状体核中的钙沉淀，这是一种可能导致这种年龄相关性白内障模型中病理性光散射的新机制。
