SPARC Deficiency Results in Improved Surgical Survival in a Novel Mouse Model of Glaucoma Filtration Surgery 英文参考文献.docVIP

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SPARC Deficiency Results in Improved Surgical Survival in a Novel Mouse Model of Glaucoma Filtration Surgery 英文参考文献.doc

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SPARC Deficiency Results in Improved Surgical Survival in a Novel Mouse Model of Glaucoma Filtration Surgery 英文参考文献

SPARCDeficiencyResultsinImprovedSurgicalSurvival inaNovelMouseModelofGlaucomaFiltrationSurgery Li-FongSeet1,RoselineSu1,V.A.Barathi1,WingSumLee1,RebekahPoh1,YeeMengHeng4,EdManser4, ErangaN.Vithana5,TinAung2,3,5,MattWeaver6,E.HeleneSage6,TinaT.Wong1,2,3* 1OcularWoundHealingandTherapeuticsGroup,SingaporeEyeResearchInstitute,Singapore,Singapore,2DepartmentofGlaucoma,SingaporeNationalEyeCentre, Singapore, Singapore, 3Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, 4Institute of Medical Biology, Agency for Science, TechnologyandResearch(A*STAR),Singapore,Singapore,5OcularGeneticsGroup,SingaporeEyeResearchInstitute,Singapore,Singapore, 6TheBenaroyaResearch InstituteatVirginiaMason,Seattle,Washington,UnitedStatesofAmerica Abstract Glaucomaisadiseasefrequentlyassociatedwithelevatedintraocularpressurethatcanbealleviatedbyfiltrationsurgery. However, thepost-operative subconjunctival scarring response which blocks filtration efficiency is amajor hurdle tothe achievementoflong-termsurgicalsuccess.Currentapplicationofanti-proliferativestomodulatethescarringresponseis notidealastheseoftengiverisetosight-threateningcomplications.SPARC(secretedprotein,acidicandrichincysteine)isa matricellularproteininvolvedinextracellularmatrix(ECM)productionandorganization.Inthisstudy,weinvestigatedpost- operativesurgicalwoundsurvivalinanexperimentalglaucomafiltrationmodelinSPARC-nullmice.LossofSPARCresulted inamarked (87.5%)surgicalwoundsurvival ratecomparedto0%inwild-type(WT)counterparts. ThelargerSPARC-null woundsimpliedthataqueousfiltrationthroughthesubconjunctivalspacewasmoreefficientincomparisontoWTwounds. The pronounced increase in both surgical survival and filtration efficiency was associated with a less collagenous ECM, smallercollagenfibrildiameter,andaloosely-organizedsubconjunctivalmatrixintheSPARC-nullwounds.Incontrast,WT wounds exhibited a densely packed collagenous ECM with no evidence of filtration capacity. Immunolocalizati