title: 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.affiliation: Department of Medicine, University of Alabama, Birmingham, Alabama, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Solomon
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Francis
authors.affiliation: Massachusetts General Hospital and Wellman Center for Photomedicine, Boston, Massachusetts, USA.
authors.forename: Kengyeh K
authors.initials: KK
authors.lastname: Chu
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, Alabama, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Birket
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: George
authors.initials: G
authors.lastname: Gabriel
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, Alabama, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Trombley
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Lemke
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Klena
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, Alabama, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Turner
authors.affiliation: Massachusetts General Hospital and Wellman Center for Photomedicine, Boston, Massachusetts, USA.
authors.forename: Guillermo J
authors.initials: GJ
authors.lastname: Tearney
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Cecilia W
authors.initials: CW
authors.lastname: Lo
authors.affiliation: Department of Medicine, University of Alabama, Birmingham, Alabama, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rowe
mesh_terms: D000818:Animals; D002923:Cilia / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007619:Kartagener Syndrome / Q000503:physiopathology; D008297:Male; D051379:Mice; D010641:Phenotype; D041623:Tomography, Optical Coherence / Q000379:methods*