May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Local TNF–alpha inhibition prevents blood–ocular barrier changes and intraocular leakage in endotoxin–induced uveitis
Author Affiliations & Notes
  • T.U. Krohne
    Center of Ophthalmology, University of Cologne, D–50931 Cologne, Germany
  • N. Kociok
    Center of Ophthalmology, University of Cologne, D–50931 Cologne, Germany
  • C. Gavranic
    Center of Ophthalmology, University of Cologne, D–50931 Cologne, Germany
  • S. Fauser
    Center of Ophthalmology, University of Cologne, D–50931 Cologne, Germany
  • V. Poulaki
    Massachussets Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • B. Kirchhof
    Center of Ophthalmology, University of Cologne, D–50931 Cologne, Germany
  • A.M. Joussen
    Center of Ophthalmology, University of Cologne, D–50931 Cologne, Germany
  • Footnotes
    Commercial Relationships  T.U. Krohne, None; N. Kociok, None; C. Gavranic, None; S. Fauser, None; V. Poulaki, None; B. Kirchhof, None; A.M. Joussen, None.
  • Footnotes
    Support  Köln Fortune, Kämpgen, DFG Jo 324 /6–1, DFG Jo 324 / 4–1, DFG Ki 734 2–1
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 578. doi:
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      T.U. Krohne, N. Kociok, C. Gavranic, S. Fauser, V. Poulaki, B. Kirchhof, A.M. Joussen; Local TNF–alpha inhibition prevents blood–ocular barrier changes and intraocular leakage in endotoxin–induced uveitis . Invest. Ophthalmol. Vis. Sci. 2004;45(13):578.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose:Breakdown of the blood–ocular barrier is one of the major problems in ocular inflammation, leading to protein leakage into the aqueous humor and formation of macular edema. Tight junctions have been demonstrated to be the main functional component of the blood–ocular barrier. Here we investigate the alterations of tight junction protein expression in retina and ciliary body tissue and the role of TNF–alpha in this process. Methods:In a rat model of LPS–induced uveitis, protein and mRNA expression of occludin and claudin–1 were examined in retina and ciliary body tissue samples by immunoblotting and quantitative real–time RT–PCR. Immunofluorescence histochemistry of flat–mounted retina and ciliary body preparations was employed to detect the tight junction protein occludin. Functional analysis of blood–ocular barrier permeability was performed using the Evans blue leakage assay. TNF–alpha was inhibited during the course of uveitis by intravitreal injection of a recombinant TNF receptor (etanercept). Results:In retina and ciliary body of LPS–treated rats the protein and mRNA content of occludin was reduced by about half while the content of claudin–1 increased about 2–3fold. Occludin immunoreactivity was diminished in the ciliary body epithelium of LPS–treated animals. Concomitant with tight junction changes, blood–ocular barrier permeability increased about 7fold. Local inhibition of TNF–alpha significantly reduced the uveitis–induced changes in occludin expression and barrier permeability. Conclusions:The current study demonstrates that the increased blood–ocular barrier permeability in experimental uveitis correlates with changes in tight junction protein expression. Local inhibition of TNF–alpha by intravitreal application of etanercept reverses these changes and restores ocular barrier function. These data underscore the role of TNF–alpha in blood–ocular barrier breakdown and the potential utility of intravitreal etanercept in the treatment of ocular inflammatory diseases.

Keywords: cell adhesions/cell junctions • cytokines/chemokines • uveitis–clinical/animal model 
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