May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Role of Microtubules in TNF- -Induced Loss of Barrier Integrity of Corneal Endothelium
Author Affiliations & Notes
  • M. Shivanna
    Optometry, Indiana Univ Sch of Optometry, Bloomington, Indiana
  • S. P. Srinivas
    Optometry, Indiana Univ Sch of Optometry, Bloomington, Indiana
  • Footnotes
    Commercial Relationships  M. Shivanna, None; S.P. Srinivas, None.
  • Footnotes
    Support  FACULTY RESEARCH GRANT, IU BLOOMINGTON, IN, (SPS)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3948. doi:https://doi.org/
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    • Get Citation

      M. Shivanna, S. P. Srinivas; Role of Microtubules in TNF- -Induced Loss of Barrier Integrity of Corneal Endothelium. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3948. doi: https://doi.org/.

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

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Abstract

Purpose: : TNF-α is a pro-inflammatory cytokine implicated in corneal endothelial failure during graft rejection. It is known to induce a loss in barrier integrity of the corneal endothelial cells but the underlying molecular mechanisms are not well understood. In this study, we have investigated the role of microtubules in TNF-α-induced loss of barrier integrity in cultured bovine corneal endothelial cells.

Methods: : Changes in the organization of actin cytoskeleton and microtubules were examined by staining for actin and α-tubulin, respectively. Localization of ZO-1, a marker of TJ assembly, was visualized by immunostaining. Changes in the barrier function were monitored continuously by transendothelial electrical resistance (TER) using ECIS (Applied Biophysics, Inc, NY).

Results: : Exposure to TNF-α (20 ng/ml; 6hr) induced disruption of microtubules along with thinning of PAMR (peri-junctional actomyosin ring) and dispersion of ZO-1. Similar exposure to TNF-α also led to a continued decline in TER, which sustained for more than 15 hr. These effects of TNF-α were significantly opposed by pretreatment with paclitaxel ( 10 µM; 1 hr), a microtubule stabilizing agent and SB 203580 (20 µM; 1 hr), a p38 MAPK (mitogen activated protein kinase) inhibitor.

Conclusions: : TNF-α may induce loss of barrier integrity through microtubule disassembly and thinning of PAMR. These events appear to be downstream of activation of p38 MAPK.

Keywords: cornea: endothelium • inflammation • cell adhesions/cell junctions 
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