Effect of tumor necrosis factor α on rabbit corneal endothelial permeability

Mitchell Aaron Watsky, Zhiwei Guan, Daniel N. Ragsdale

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Abstract

Purpose. Tumor necrosis factor a (TNFα) is present in the iris and the lacrimal gland, and its concentration is increased during inflammation and after corneal wounding. Although TNFα has been shown to increase keratocyte and corneal epithelial interleukin production, no definitive effects of TNFα on corneal endothelial cells have been reported. TNFα has been shown to disrupt barrier function in vascular endothelial monolayers through f- actin depolymerization. A reduction in intracellular cyclic adenosine monophosphate (cAMP) concentration may play a role in this response. This study was designed to examine the role and signal transduction mechanisms of TNFα modulation of endothelial permeability in the cornea. In addition, it is the first examination of the effects of TNFα on the barrier function of a noncultured cell monolayer. Methods. Rabbit corneal endothelial superfusions were performed under an in vitro specular microscope. Corneas were processed for permeability measurements or f-actin staining. Results. TNFα superfused corneas had significantly higher permeabilities than controls. f-actin staining revealed that TNFα superfusion disrupted f- actin filaments when compared to controls. Corneas superfused with the f- actin stabilizing agent phallacidin had significantly lower permeabilities than TNFα superfused pairs. Permeabilities of corneas superfused with TNFα plus 8-bromo-cAMP (0.01 to 3 mM) were significantly lower than TNFα superfused pairs at all concentrations, although only significantly lower at the 0.1 mM cAMP concentration. Conclusions. TNFα causes an increase in corneal endothelial permeability, and this increase is mediated by disruption of f-actin filaments; cAMP appears to be involved in this response.

Original languageEnglish (US)
Pages (from-to)1924-1929
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number9
Publication statusPublished - Aug 1 1996
Externally publishedYes

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Keywords

  • cornea
  • cyclic adenosine monophosphate
  • endothelium
  • permeability
  • tumor necrosis factor α

ASJC Scopus subject areas

  • Ophthalmology

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