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

Publication ,  Journal Article
Tam, LCS; Reina-Torres, E; Sherwood, JM; Cassidy, PS; Crosbie, DE; Lütjen-Drecoll, E; Flügel-Koch, C; Perkumas, K; Humphries, MM; Kiang, A-S ...
Published in: Sci Rep
January 16, 2017

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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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

January 16, 2017

Volume

7

Start / End Page

40717

Location

England

Related Subject Headings

  • Tight Junctions
  • RNA, Small Interfering
  • RNA Interference
  • Primates
  • Permeability
  • Mice
  • Immunohistochemistry
  • Humans
  • Gene Expression
  • Endothelium
 

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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. Sci Rep, 7, 40717. https://doi.org/10.1038/srep40717
Tam, Lawrence C. S., Ester Reina-Torres, Joseph M. Sherwood, Paul S. Cassidy, Darragh E. Crosbie, Elke Lütjen-Drecoll, Cassandra Flügel-Koch, et al. “Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia.Sci Rep 7 (January 16, 2017): 40717. https://doi.org/10.1038/srep40717.
Tam LCS, Reina-Torres E, Sherwood JM, Cassidy PS, Crosbie DE, Lütjen-Drecoll E, et al. Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia. Sci Rep. 2017 Jan 16;7:40717.
Tam, Lawrence C. S., et al. “Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia.Sci Rep, vol. 7, Jan. 2017, p. 40717. Pubmed, doi:10.1038/srep40717.
Tam LCS, Reina-Torres E, Sherwood JM, Cassidy PS, Crosbie DE, Lütjen-Drecoll E, Flügel-Koch C, Perkumas K, Humphries MM, Kiang A-S, O’Callaghan J, Callanan JJ, Read AT, Ethier CR, O’Brien C, Lawrence M, Campbell M, Stamer WD, Overby DR, Humphries P. Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia. Sci Rep. 2017 Jan 16;7:40717.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

January 16, 2017

Volume

7

Start / End Page

40717

Location

England

Related Subject Headings

  • Tight Junctions
  • RNA, Small Interfering
  • RNA Interference
  • Primates
  • Permeability
  • Mice
  • Immunohistochemistry
  • Humans
  • Gene Expression
  • Endothelium