Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia

Journal article


Publication Details

Author(s): Tam LCS, Reina-Torres E, Sherwood JM, Cassidy PS, Crosbie DE, Lütjen-Drecoll E, Flügel-Koch C, Perkumas K, Humphries MM, Kiang AS, O'Callaghan J, Callanan JJ, Read AT, Ethier CR, O'Brien C, Lawrence M, Campbell M, Stamer WD, Overby DR, Humphries P
Journal: Scientific Reports
Publication year: 2017
Volume: 7
ISSN: 2045-2322


Abstract

The juxtacanalicular connective tissue of the trabecular meshwork together with inner wall endothelium of Schlemm's canal (SC) provide the bulk of resistance to aqueous outflow from the anterior chamber. Endothelial cells lining SC elaborate tight junctions (TJs), down-regulation of which may widen paracellular spaces between cells, allowing greater fluid outflow. We observed significant increase in paracellular permeability following siRNA-mediated suppression of TJ transcripts, claudin-11, zonula-occludens-1 (ZO-1) and tricellulin in human SC endothelial monolayers. In mice claudin-11 was not detected, but intracameral injection of siRNAs targeting ZO-1 and tricellulin increased outflow facility significantly. Structural qualitative and quantitative analysis of SC inner wall by transmission electron microscopy revealed significantly more open clefts between endothelial cells treated with targeting, as opposed to non-targeting siRNA. These data substantiate the concept that the continuity of SC endothelium is an important determinant of outflow resistance, and suggest that SC endothelial TJs represent a specific target for enhancement of aqueous movement through the conventional outflow system.


FAU Authors / FAU Editors

Flügel-Koch, Cassandra Prof. Dr.
Medizinische Fakultät
Lütjen-Drecoll, Elke Prof. Dr.
Lehrstuhl für Anatomie II


External institutions with authors

Duke University
Georgia Institute of Technology
Imperial College London / The Imperial College of Science, Technology and Medicine
Ross University School of Veterinary Medicine
RxGen, Inc.
Trinity College Dublin
University College Dublin (UCD)
University of Toronto


How to cite

APA:
Tam, L.C.S., Reina-Torres, E., Sherwood, J.M., Cassidy, P.S., Crosbie, D.E., Lütjen-Drecoll, E.,... Humphries, P. (2017). Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia. Scientific Reports, 7. https://dx.doi.org/10.1038/srep40717

MLA:
Tam, Lawrence C. S., et al. "Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia." Scientific Reports 7 (2017).

BibTeX: 

Last updated on 2019-28-02 at 06:13