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

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

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Article number40717
JournalScientific reports
Volume7
DOIs
StatePublished - Jan 16 2017
Externally publishedYes

ASJC Scopus subject areas

  • General

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