Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography
George M. Solomon, Richard Francis, Kengyeh K. Chu, Susan E. Birket, George Gabriel, John E. Trombley, Kristi L. Lemke, Nikolai Klena, Brett Turner, Guillermo J. Tearney, Cecilia W. Lo, Steven M. Rowe
George M. Solomon, Richard Francis, Kengyeh K. Chu, Susan E. Birket, George Gabriel, John E. Trombley, Kristi L. Lemke, Nikolai Klena, Brett Turner, Guillermo J. Tearney, Cecilia W. Lo, Steven M. Rowe
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Research Article Pulmonology

Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography

Abstract

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). Ccdc39–/– mice, with a known severe PCD mutation of ciliary axonemal organization, had absent motile ciliary regions, resulting in abrogated MCT. In contrast, Dnah5–/– 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. Wdr69–/– 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.

Authors

George M. Solomon, Richard Francis, Kengyeh K. Chu, Susan E. Birket, George Gabriel, John E. Trombley, Kristi L. Lemke, Nikolai Klena, Brett Turner, Guillermo J. Tearney, Cecilia W. Lo, Steven M. Rowe

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Figure 2

Pathological characterization of PCD mice.

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Pathological characterization of PCD mice. (A) Representative pathologic...
(A) Representative pathological sections from Ccdc39–/– mice (n = 5). (B) Representative pathological sections from Dnah5–/– mice (n = 5). (C) Representative pathological sections from Wdr69–/– mice. (A–C) Situs inversus is demonstrated when the cardiac axis is rightward and the spleen and liver are reversed in the abdomen. Number designations indicate organ laterality (1, lobes of the liver; 2, the hepatic vein; 3, the spleen). Black arrows indicate the axis of the heart. Stm, stomach. Scale bar: 0.2 mm. (D) Representative electron micrograph of cilium indicating normal expression of outer dynein arms (black arrowheads, n = 10) in Wdr69+/+ mice compared with (E) Wdr69–/– mice, demonstrating reduced expression of outer dynein arms. Scale bar: 100 mm.