PURPOSE: Gap junction intercellular communication (GJIC) plays a critical role in the maintenance of corneal endothelium homeostasis. We determined if @entity3676 (BAK) alters GJIC activity in the @entity95 corneal endothelium since it is commonly used as a drug preservative in ocular eyedrop preparations even though it can have cytotoxic effects. METHODS: Thirty-six adult New Zealand albino @entity95 were randomly divided into three groups. BAK at 0.01%, 0.05%, and 0.1% was applied twice daily to one eye of each of the @entity95 in one of the three groups for seven days. The contralateral untreated eyes were used as controls. Corneal endothelial morphological features were observed by in vivo confocal microscopy (IVCM). Immunofluorescent staining resolved changes in gap junction integrity and localization. Western blot analysis and RT-PCR evaluated changes in levels of @entity1006 ( @entity1006 ) and tight junction zonula occludens-1 (ZO-1) gene and protein expression, respectively. @entity1006 and ZO-1 physical interaction was detected by immunoprecipitation (IP). Primary @entity95 corneal endothelial cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing BAK for 24 hours. The scrape-loading dye transfer technique (SLDT) was used to assess GJIC activity. RESULTS: Topical administration of BAK (0.05%, 0.1%) dose dependently disrupted corneal endothelial cell morphology, altered @entity1006 and ZO-1 distribution and reduced @entity1006 expression. BAK also markedly induced increases in @entity1006 phosphorylation status concomitant with decreases in the @entity1006 -ZO-1 protein-protein interaction. These changes were associated with marked declines in GJIC activity. CONCLUSIONS: The dose dependent declines in @entity95 corneal endothelial GJIC activity induced by BAK are associated with less @entity1006 -ZO-1 interaction possibly arising from increases in @entity1006 phosphorylation and declines in its protein expression. These novel changes provide additional evidence that BAK containing eyedrop preparations should be used with caution to avoid declines in corneal transparency resulting from losses in GJIC activity and endothelial function.

XXXX suppresses @entity95 corneal endothelium intercellular gap junction communication.

@entity95 :: ('9986', 'Species') :: ['rabbits', 'rabbit'] @entity3676 :: ('MESH:D001548', 'Chemical') :: ['benzalkonium chloride'] @entity1006 :: ('100008935(Tax:9986)', 'Gene') :: ['connexin43', 'Cx43']
@entity3676 :: (MESH:D001548,Chemical) :: ['Benzalkonium chloride']
