*** of cyclic-AMP-response element binding protein and its impact on corneal wound healing in vitro and in vivo
作者机构:Département d'ophtalmologieUniversitéLavalCUO-recherche/LOEXCentre de recherche du CHU de Québec-UniversitéLavalQuébecQCCanada Département de chirurgieUniversitéLavalCentre de recherche en organogénèse expérimentale de l’UniversitéLaval/LOEXCentre de recherche du CHU de Québec-UniversitéLavalQuébecQCCanada
出 版 物:《Annals of Eye Science》 (眼科学年鉴(英文))
年 卷 期:2019年第1期
页 面:195-195页
主 题:Cyclic-AMP-response element binding protein(CREB) protein kinase B(AKT) healing corneal wound tissue-engineering
摘 要:Background:The cornea composes the outer surface of the eye and its transparency is required to allow light transmission to the ***,because of its position,the cornea is subjected to chemical and mechanical injuries that may lead to *** studies conducted using the human tissue-engineered cornea(hTEC)as a model provided evidence that the cyclic-AMP-response element binding protein(CREB)pathway is repressed during closure of corneal *** on these results,we hypothesized that closure of corneal wounds can be enhanced by preventing activation of CREB with the pharmacological inhibitor *** goals were to proceed to the pharmacological inhibition of CREB(I)in vitro using the hTECs as a model,and then(II)in vivo using the rabbit as a ***:The self-assembly approach was used to create hTECs,that were then wounded with an 8-mm diameter biopsy punch to create an epithelial *** tissues were then incubated with 10μM of C646(n=8).DMSO was used alone as a negative control(n=4).Closure of the wounds was monitored over a period of 5 ***,the cornea of New Zealand white rabbits was debrided with an ethanol 70%solution to create an epithelial defect of 8-mm *** concentrations of C646(1,10,100μM et 1 mM)were applied as eye drops 3 times a day for up to 7 *** wounded corneas(n=4 per concentration)were stained with fluorescein and photographed every ***:In vitro pharmacological inhibition of CREB with C646 considerably accelerated wound closure of all treated hTECs(4 days)compared to the control group(7 days).Moreover,the in vivo C646 treatment also accelerated wound healing of the corneas compared to the control *** most effective concentration of C646 tested was the lowest(1μM),as it considerably enhanced the wound healing ***:This study demonstrates that wound healing both in vitro and in vivo can be enhanced by preventing activation of CREB using a pharmacological inhibition appr