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

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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.

Item Type: Article
Divisions: Faculty of Health Sciences and Wellbeing
Depositing User: Matthew Campbell
Date Deposited: 24 Feb 2021 11:06
Last Modified: 24 Feb 2021 11:06
URI: http://sure.sunderland.ac.uk/id/eprint/13134
ORCID for Matthew Campbell: ORCID iD orcid.org/0000-0001-5883-5041

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