Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase 英文参考文献.docVIP

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Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase 英文参考文献.doc

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SelectiveInhibitionofRetinalAngiogenesisbyTargeting PI3Kinase YolandaAlvarez1*,OlayaAstudillo1,LasseJensen2,AlisonL.Reynolds1,NoraWaghorne1,DerekP. Brazil3,YihaiCao2,JohnJ.O’Connor1,Breanda′nN.Kennedy1* 1UCDSchoolsofBiomolecularandBiomedicalSciences,UCDConwayInstitute,UniversityCollegeDublin,Dublin,Ireland,2InstituteforMicrobiologyTumorandCell Biology, Karolinska Institute, Stockholm, Sweden, 3Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast,Belfast,UnitedKingdom Abstract Ocularneovascularisationisapathologicalhallmarkofsomeformsofdebilitatingblindnessincludingdiabeticretinopathy, age related macular degeneration and retinopathy of prematurity. Current therapies for delaying unwanted ocular angiogenesis include laser surgery or molecular inhibition of the pro-angiogenic factor VEGF. However, targeting of angiogenicpathwaysotherthan,orincombinationtoVEGF,mayleadtomoreeffectiveandsaferinhibitorsofintraocular angiogenesis.Inasmallchemicalscreenusingzebrafish,weidentifyLY294002asaneffectiveandselectiveinhibitorofboth developmental and ectopic hyaloid angiogenesis in the eye. LY294002, a PI3 kinase inhibitor, exerts its anti-angiogenic effect in a dose-dependent manner, without perturbing existing vessels. Significantly, LY294002 delivered by intraocular injection,significantlyinhibitsocularangiogenesiswithoutsystemicside-effectsandwithoutdiminishingvisualfunction. Thus,targetingofPI3kinasepathwayshasthepotentialtoeffectivelyandsafelytreatneovascularisationineyedisease. Citation: Alvarez Y, Astudillo O, Jensen L, Reynolds AL, Waghorne N, et al. (2009) Selective Inhibition of Retinal Angiogenesis by Targeting PI3 Kinase. PLoS ONE4(11):e7867.doi:10.1371/journal.pone.0007867 Editor:RafaelLinden,UniversidadeFederaldoRiodeJaneiro(UFRJ),InstitutodeBiof?′sicadaUFRJ,Brazil ReceivedAugust10,2009;AcceptedOctober9,2009;PublishedNovember17,2009 Copyright: ? 2009 Alvarez et al. This is an open-access article dist