Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-1-4
pubmed:abstractText
The main goal of the present study was to investigate the response of cultured bovine corneas to the application of irritant substances and its potential use for predicting ocular irritancy in humans. We hypothesized that chemicals causing eye irritation may induce disruption of epithelial tight junctions and trigger cell stress responses modulated via transcription factors such as AP-1 and NF-kappaB. A simple air-lifted corneal organ culture system was used as an ex vivo model for ocular irritancy test. The effects of two surfactants, sodium dodecyl sulfate (SDS) and benzalkonium chloride (BAK), on corneal epithelial permeability and DNA-binding activity of AP-1 and NF-kappaB were studied in cultured bovine corneas. Both SDS and BAK induced tight junction disruption and increased permeability of corneal epithelium assessed using surface biotinylation in a concentration- and time-dependent manner. An increase in DNA-binding activity measured using electrophoretic mobility shift assay was observed when cultured corneas were treated with surfactants at concentrations causing minimal to mild ocular irritation, indicating epithelial cell stress response. Furthermore, exposure of cultured corneas to SDS or BAK at concentrations causing severe ocular irritancy resulted in a decrease in DNA-binding activity of these transcription factors in epithelial cells. These results indicate that the combination of corneal organ culture and measurements of corneal epithelial permeability and DNA-binding activity of stress-response transcription factors following chemical exposure has the potential to be used as a mechanistically based alternative to in vivo animal testing.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
306-14
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Corneal organ culture model for assessing epithelial responses to surfactants.
pubmed:affiliation
The Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, Massachusetts 02114, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't