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*** of beta-adrenergic receptor in choroidal neovascularization

Annals of Eye Science 2018年第1期 439-439页

作者： Houda Tahiri Samy Omri isabelle lahaie Sylvain Chemtob Research Center Hôpital Maisonneuve-Rosemont Universitéde MontréalMontréalQCCanada Research Center CHU Sainte-Justine Universitéde MontréalMontréalQCCanada Department of Pharmacology Universitéde MontréalMontréalQCCanada Department of Ophthalmology Universitéde MontréalMontréalQCCanada Department of Pediatrics Universitéde MontréalMontréalQCCanada

Background:We investigated the role of beta-adrenergic receptor(B-AR)on choroidal neovascularization(CNV)in an animal model of age-related macular degeneration in ***:The angiogenic effect of the B-AR was evaluated in retinal pigment epithelium(RPE)-choroid explants from C57Bl6 mice stimulated with propranolol or isoproterenol(10μM)(respectively antagonist and agonist of the B-AR)during 24 ***,a classic choroidal neovascularization(CNV)model induced by laser burn in C57Bl6 mice(8 weeks)was used to assess the anti-angiogenic effect of *** this experiment,mice were treated with intraperitoneal propranolol(6 mg/kg/d)or vehicle(saline solution)daily for 10 days,starting on day 4 after laser burn and until sacrifice(day 14).Immunostaining analysis on retinal flatmounts and cryosections were performed to determine the surface of CNV,the distribution of B-AR and the number and morphology of microglia/macrophages associated with *** explore if the antiangiogenic effect of propranolol involved the modulation of the inflammatory microenvironment associated with CNV,we used RPE primary cells,J774 macrophages cell line and polarized M1 and M2 bone marrow-derived macrophage(BMDM).Choroidal explants treated with conditioned media(CM)from J774 or polarized M1/M2 BMDM pre-treated with propranolol to confirm the anti-angiogenic effect of *** of angiogenic factors was evaluated by RT PCR and ***:The expression and distribution of the B-1,B-2 and B-3 adrenergic receptors were localized in the choroid and RPE *** stimulation of RPE-choroid explants with isoproterenol increased CNV compared to vehicle,while propranolol decreased *** vivo,propranolol inhibited significantly the levels of VEGF and CNV growth in laser burn model compared to the ***,the treatment with propranolol decremented the number of activated(amoeboid shape)microglia/macrophages but surprisingly,the number of non-activated microglia

关键词： Choroidal neovascularization(CNV) macrophages beta-adrenergic receptor(B-AR)

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

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Annals of Eye Science 2019年第1期 217-217页

作者： Michel Desjarlais Jose Carlos Rivera isabelle lahaie Maëlle Wirt Sylvain Chemtob Department of Ophthalmology Maisonneuve-Rosemont Hospital Research CenterUniversity of MontréalMontréalQCCanada Departments of Pediatrics Ophthalmology and PharmacologyCentre Hospitalier Universitaire Sainte-Justine Research CenterMontréalQCCanada

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

关键词： Ischemic retinopaty miRNA angiogenesis vascular repair hyperoxia

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

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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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