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***-standing choroidal thinning in oxygen-induced retinopathy

Annals of Eye Science 2018年第1期 449-449页

作者： Tianwei Ellen Zhou Tang Zhu Houda Tahiri Samy Omri JoséCarlos Rivera Isabelle Lahaie cheri deal Stanley Nattel Sylvain Chemtob Department of Pharmacology McGill UniversityMontréalQCCanada Department of Pharmacology Universitéde MontréalMontréalQCCanada Research Center Hôpital Maisonneuve-Rosemont Universitéde MontréalMontréalQCCanada Research Center CHU Sainte-Justine Universitéde MontréalMontréalQCCanada Department of Pediatrics Universitéde MontréalMontréalQCCanada Department of Ophthalmology Universitéde MontréalMontréalQCCanada

Background:Retinopathy of prematurity(ROP),the most common cause of blindness in premature infants,has long been associated with pathologic retinal ***,recent studies reveal choroidal involution in adolescent patients formerly afflicted with *** have recently demonstrated that choroidal thinning occurs early in retinopathy and persists into *** retinal vessels,the damaged choroidal vasculature in ROP is incapably to ***,we investigated the molecular mechanism implicated in the lack of choroidal repair in ischemic ***:The oxygen-induced retinopathy(OIR)model was *** Sprague-Dawley(albino)or Long-Evans rats(pigmented)rats were placed under oxygen concentration which cycles at 50%±1%or 10%±1%every 24 hours(hr)from postnatal day(P)0 to *** P14,all rats were returned to room *** blotting and qPCR were used to quantify protein and RNA abundances,*** Dual-Luciferase®Reporter Assay System was used to confirm microRNA(miRNA)-mRNA ***:We detected a substantial oxidative stress in retinal pigment epithelium(RPE)and choroidal tissue,accompanied by a drastic reduction in insulin-like growth factor 1 receptor(IGF1R),a critical player in post-injury *** mechanism of decreasing IGF1R involves the over-activation of the p53 tumor suppressor that regulates miRNA let-7b,which subsequently silences Igf1r mRNA in the RPE/choroid complex of OIR *** reporter assay confirmed that let-7b directly targets Igf1r mRNA at its 3’untranslated region(UTR).Indeed,silencing p53 resulted in a decreased let-7b expression,and re-established IGF1R abundance that promoted choroidal ***:Together,this study sets forth new mechanistic notion by uncovering the novel p53/let-7b/IGF1R axis;timely intervention of this pathway facilitates healthy choroidal *** investigations on anti-angiogenic miRNAs can better our understanding

关键词： Choroid retinopathy of prematurity(ROP) p53 microRNA

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