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M A Watsky, Z Guan, D N Ragsdale; Effect of tumor necrosis factor alpha on rabbit corneal endothelial permeability.. Invest. Ophthalmol. Vis. Sci. 1996;37(9):1924-1929.
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PURPOSE: Tumor necrosis factor alpha (TNF alpha) is present in the iris and the lacrimal gland, and its concentration is increased during inflammation and after corneal wounding. Although TNF alpha has been shown to increase keratocyte and corneal epithelial interleukin production, no definitive effects of TNF alpha on corneal endothelial cells have been reported. TNF alpha 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 TNF alpha modulation of endothelial permeability in the cornea. In addition, it is the first examination of the effects of TNF alpha 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: TNF alpha superfused corneas had significantly higher permeabilities than controls. f-actin staining revealed that TNF alpha superfusion disrupted f-actin filaments when compared to controls. Corneas superfused with the f-actin stabilizing agent phallacidin had significantly lower permeabilities than TNF alpha superfused pairs. Permeabilities of corneas superfused with TNF alpha plus 8-bromo-cAMP (0.01 to 3 mM) were significantly lower than TNF alpha superfused pairs at all concentrations, although only significantly lower at the 0.1 mM cAMP concentration. CONCLUSIONS: TNF alpha 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.
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