Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
This PDF is available to Subscribers Only