Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye A Computer Simulation Study 英文参考文献.docVIP

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Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye A Computer Simulation Study 英文参考文献.doc

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Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye A Computer Simulation Study 英文参考文献

AdhesionFailuresDeterminethePatternofChoroidal NeovascularizationintheEye:AComputerSimulation Study AbbasShirinifard1*,JamesAlexanderGlazier1,MaciejSwat1,J.ScottGens1,FereydoonFamily2, YiJiang3,4,HansE.Grossniklaus5 1The Biocomplexity Institute and Department of Physics, Indiana University Bloomington, Bloomington, Indiana, United States of America, 2Department of Physics, Emory University, Atlanta, Georgia, United States ofAmerica,3DepartmentofMathematicsandStatistics, GeorgiaStateUniversity,Atlanta,Georgia, United States of America,4TheoreticalDivision,LosAlamosNationalLaboratory,LosAlamos,NewMexico,UnitedStatesofAmerica,5L.F.MontgomeryOphthalmicPathologyLaboratory, EmoryUniversity,Atlanta,Georgia,UnitedStatesofAmerica Abstract Choroidalneovascularization(CNV)ofthemacularareaoftheretinaisthemajorcauseofseverevisionlossinadults.InCNV, afterchoriocapillariesinitiallypenetrateBruch’smembrane(BrM),invadingvesselsmayregressorexpand(CNVinitiation). Next,duringEarlyandLateCNV,theexpandingvasculatureusuallyspreadsinoneofthreedistinctpatterns:inalayerbetween BrMandtheretinalpigmentepithelium(sub-RPEorType1CNV),inalayerbetweentheRPEandthephotoreceptors(sub- retinalorType2CNV)orinbothlocisimultaneously(combinedpatternorType3CNV).Whilemoststudieshypothesizethat CNVprimarilyresultsfromgrowth-factoreffectsorholesinBrM,ourthree-dimensionalsimulationsofmulti-cellmodelofthe normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complextoBrM(RPE-BrMadhesion),and3)AdhesionoftheRPEtothephotoreceptoroutersegments(RPE-POSadhesion). OurkeyfindingsarethatwhenanendothelialtipcellpenetratesBrM:1)RPEwithnormalepithelialjunctions,basalattachment toBrMandapicalattachmenttoPOSresistsCNV.2)SmallholesinBrMdonot,bythemselves,initiateCNV.3)RPEwithnormal epithelialjunctionsandnormalapicalRPE-POSadhesion,butweakadhesiontoB