Journal
EXPERIMENTAL EYE RESEARCH
Volume 89, Issue 6, Pages 950-959Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2009.08.004
Keywords
corneal endothelium; TNF-alpha; barrier integrity; microtubules; paclitaxel
Categories
Funding
- NIH [R21-EY019119]
- Faculty Research Grant, VP of Research, IU Bloomington, IN
- IU Bloomington
- IN
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Microtubule disassembly breaks down the barrier integrity in a number of epithelial and endothelial monolayers. This study has investigated effects of TNF-alpha, which is implicated in corneal allograft rejection, on microtubules and barrier integrity in cultured bovine corneal endothelial cells. Exposure to TNF-alpha led to disassembly of the microtubules, and also caused disruption of the perijunctional actomyosin ring (PAMR). As a measure of barrier integrity, trans-endothelial electrical resistance (TER) was determined based on electrical cell-substrate impedance sensing in realtime. Exposure to TNF-alpha caused a slow decline in TER for > 20 h, and a similar exposure to cells grown on porous culture inserts led to a significant increase in permeability to FITC dextran. These changes, indicating a loss of barrier integrity, were also reflected by dislocation of ZO-1 at the cell border and disassembly of cadherins. These effects of TNF-alpha were inhibited upon stabilization of microtubules by pre-treatment with paclitaxel or epothilone B. Microtubule stabilization may be a useful strategy to overcome (TNF-alpha)-induced loss of the barrier integrity of corneal endothelium during inflammation associated with transplant rejection and uveitis. (C) 2009 Elsevier Ltd. All rights reserved.
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