AB042.microRNA-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 

机构地区：[1]Department of Ophthalmology,Maisonneuve-Rosemont Hospital Research Center,University of Montréal,Montréal,QC,Canada [2]Departments of Pediatrics,Ophthalmology and Pharmacology,Centre Hospitalier Universitaire Sainte-Justine Research Center,Montréal,QC,Canada

出　　处：《Annals of Eye Science》2019年第1期217-217,共1页眼科学年鉴（英文）

摘　　要：Background:Ischemic retinopathies(IRs)are ocular disorders associated to microvascular degeneration leading to visual impairments and blindness.microRNA(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 NV.However,the post-transcriptional modulation of miRs and especially,their specific functions in the eyes during IRs remain to be evaluated.We 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)rats.To 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 miR-96.In 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 antagomir-96.Angiogenic assay was performed(tube formation and migration)and molecular analysis evaluated by qRT-PCR and western blot.Results:NSG and qRT-PCR analyses identified miR-96 as one of most highly expressed miRNAs in retina and choroid during development.However,miR-96 showed a strong downregulation in OIR rats,and also in HRMVEC subjected to hyperoxia.In HRMVEC,we found that miR-96 regulates positively the expression of the key pro-angiogenic factors VEGF,FGF-2 and ANG-2.To better explore the role of miR-96 on HRMVEC angiogenic activity,we performed a gain/loss of function study.Similarly,to hyperoxia exposure,we observed a robust angiogenic impairment(tube formation and migration)on HMRVEC transfected with an antagomiR-96.Interestingly,overexpression of miR-96 completely recued the basal phenotype of HRMVEC and protected against

关 键 词：Ischemic retinopaty miRNA angiogenesis vascular repair HYPEROXIA 

分 类 号：R73[医药卫生—肿瘤]