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

Tam, Lawrence C. S., Reina-Torres, Ester, Sherwood, Joseph M., Cassidy, Paul S., Crosbie, Darragh E., Lütjen-Drecoll, Elke, Flügel-Koch, Cassandra, Perkumas, Kristin, Humphries, Marian M., Kiang, Anna-Sophia, O’Callaghan, Jeffrey, Callanan, John J., Read, A. Thomas, Ethier, C. Ross, O’Brien, Colm, Lawrence, Matthew, Campbell, Matthew, Stamer, W. Daniel, Overby, Darryl R. and Humphries, Pete (2017) Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm’s Canal Endothelia. Scientific Reports, 7 (1). ISSN 2045-2322

Item Type: Article


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.

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Depositing User: Matthew Campbell


Item ID: 13134
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ISSN: 2045-2322
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ORCID for Matthew Campbell: ORCID iD

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Date Deposited: 24 Feb 2021 11:06
Last Modified: 24 Feb 2021 11:06


Author: Matthew Campbell ORCID iD
Author: Lawrence C. S. Tam
Author: Ester Reina-Torres
Author: Joseph M. Sherwood
Author: Paul S. Cassidy
Author: Darragh E. Crosbie
Author: Elke Lütjen-Drecoll
Author: Cassandra Flügel-Koch
Author: Kristin Perkumas
Author: Marian M. Humphries
Author: Anna-Sophia Kiang
Author: Jeffrey O’Callaghan
Author: John J. Callanan
Author: A. Thomas Read
Author: C. Ross Ethier
Author: Colm O’Brien
Author: Matthew Lawrence
Author: W. Daniel Stamer
Author: Darryl R. Overby
Author: Pete Humphries

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Faculty of Health Sciences and Wellbeing

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