Department of Medicine, University of Alabama, Birmingham, Alabama, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
JCI Insight. 2017 Mar 9;2(5):e91702. doi: 10.1172/jci.insight.91702.
Ciliary motion defects cause defective mucociliary transport (MCT) in primary ciliary dyskinesia (PCD). Current diagnostic tests do not assess how MCT is affected by perturbation of ciliary motion. In this study, we sought to use micro-optical coherence tomography (μOCT) to delineate the mechanistic basis of cilia motion defects of PCD genes by functional categorization of cilia motion. Tracheae from three PCD mouse models were analyzed using μOCT to characterize ciliary motion and measure MCT. We developed multiple measures of ciliary activity, integrated these measures, and quantified dyskinesia by the angular range of the cilia effective stroke (ARC). mice, with a known severe PCD mutation of ciliary axonemal organization, had absent motile ciliary regions, resulting in abrogated MCT. In contrast, mice, with a missense mutation of the outer dynein arms, had reduced ciliary beat frequency (CBF) but preserved motile area and ciliary stroke, maintaining some MCT. PCD mice exhibited normal motile area and CBF and partially delayed MCT due to abnormalities of ciliary ARC. Visualization of ciliary motion using μOCT provides quantitative assessment of ciliary motion and MCT. Comprehensive ciliary motion investigation in situ classifies ciliary motion defects and quantifies their contribution to delayed mucociliary clearance.
纤毛运动缺陷导致原发性纤毛运动障碍（PCD）中黏液纤毛转运（MCT）受损。目前的诊断测试不能评估纤毛运动的扰动如何影响 MCT。在这项研究中，我们试图使用微光学相干断层扫描（μOCT）通过纤毛运动的功能分类来描绘 PCD 基因纤毛运动缺陷的机制基础。使用 μOCT 分析来自三种 PCD 小鼠模型的气管，以表征纤毛运动并测量 MCT。我们开发了多种纤毛活动度量标准，整合了这些度量标准，并通过纤毛有效行程的角度范围（ARC）来量化运动障碍。由于纤毛轴丝组织的已知严重 PCD 突变， 小鼠缺乏可动纤毛区域，导致 MCT 中断。相比之下， 小鼠的外动力臂错义突变导致 CBF 降低，但保留了可动区和纤毛行程，维持了一些 MCT。 PCD 小鼠由于纤毛 ARC 的异常表现出正常的可动区和 CBF 以及部分延迟的 MCT。使用 μOCT 可视化纤毛运动可提供纤毛运动和 MCT 的定量评估。原位综合纤毛运动研究将纤毛运动缺陷分类，并量化其对黏液纤毛清除延迟的贡献。
