***-96-based therapy protect microvasculature against oxygen-induced retinopathy:a novel uncovered property of miR-96 in vascular repair

作     者：Michel Desjarlais Jose Carlos Rivera Isabelle Lahaie Maëlle Wirt Sylvain Chemtob 

作者机构：Department of OphthalmologyMaisonneuve-Rosemont Hospital Research CenterUniversity of MontréalMontréalQCCanada Departments of PediatricsOphthalmology and PharmacologyCentre Hospitalier Universitaire Sainte-Justine Research CenterMontréalQCCanada 

出 版 物：《Annals of Eye Science》 (眼科学年鉴（英文）)

年 卷 期：2019年第1期

页      面：217-217页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：Ischemic retinopaty miRNA angiogenesis vascular repair hyperoxia 

摘      要：Background:Ischemic retinopathies(IRs)are ocular disorders associated to microvascular degeneration leading to visual impairments and ***(miRNAs)are a family of non-coding RNAs that regulate a wide range of gene expression involved in various biological process such blood vessel development and pathological ***,the post-transcriptional modulation of miRs and especially,their specific functions in the eyes during IRs remain to be *** aim to evaluate the potential role of miR-96 on microvascular degeneration in a rat model of oxygen-induced retinopathy(OIR).Methods:In vivo:next generation sequencing(NSG)was used to perform a complete miRNAs profiling in the retina and choroid from OIR and normoxia(CTL)*** evaluate the effects of miR-96 on microvasculature,OIR animals were treated with a miR-96 mimic(1 mg/kg)or a control-miR by intravitreal injection before hyperoxia-exposure(80%O2).Immunostaining analysis of retinal flatmounts and cryosections was used to explore the microvascular effects of *** vitro:Human Retinal Microvascular Endothelial Cells(HRMVEC)were subjected or not to hyperoxia(80%O2)and transfected with 50 nM of miR-96 mimic or *** assay was performed(tube formation and migration)and molecular analysis evaluated by qRT-PCR and western ***:NSG and qRT-PCR analyses identified miR-96 as one of most highly expressed miRNAs in retina and choroid during ***,miR-96 showed a strong downregulation in OIR rats,and also in HRMVEC subjected to *** HRMVEC,we found that miR-96 regulates positively the expression of the key pro-angiogenic factors VEGF,FGF-2 and *** better explore the role of miR-96 on HRMVEC angiogenic activity,we performed a gain/loss of function ***,to hyperoxia exposure,we observed a robust angiogenic impairment(tube formation and migration)on HMRVEC transfected with an ***,overexpression of miR-96 completely recued the