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Enhancement of outflow facility in the murine eye by targeting selected tight-junctions of Schlemm's canal endothelia

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Title: Enhancement of outflow facility in the murine eye by targeting selected tight-junctions of Schlemm's canal endothelia
Authors: Tam, LC
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
Item Type: Journal Article
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.
Issue Date: 16-Jan-2017
Date of Acceptance: 9-Dec-2016
URI: http://hdl.handle.net/10044/1/44107
DOI: http://dx.doi.org/10.1038/srep40717
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 7
Copyright Statement: © 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
National Institutes of Health
Fight For Sight
National Institutes of Health
Funder's Grant Number: EP/J010499/1
203-1774
Ref: 1385
SP0028943-PROJ0007600
Publication Status: Published
Conference Place: England
Article Number: 40717
Appears in Collections:Bioengineering
Faculty of Engineering