Cellular Signaling and Potential New Treatment Targets in Diabetic Retinopathy英文文献资料.docVIP

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Cellular Signaling and Potential New Treatment Targets in Diabetic Retinopathy英文文献资料.doc

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Cellular Signaling and Potential New Treatment Targets in Diabetic Retinopathy英文文献资料

HindawiPublishingCorporation ExperimentalDiabetesResearch Volume2007,ArticleID31867,12pages doi:10.1155/2007/31867 ReviewArticle CellularSignalingandPotentialNewTreatmentTargetsin DiabeticRetinopathy ZiaA.KhanandSubrataChakrabarti Received28December2006;Revised2May2007;Accepted13September2007 RecommendedbyTimothyKern Dysfunctionanddeathofmicrovascularcellsandimbalancebetweentheproductionandthedegradationofextracellularmatrix (ECM)proteinsareacharacteristicfeatureofdiabeticretinopathy(DR).Glucose-inducedbiochemicalalterationsinthevascu- larendothelialcellsmayactivateacascadeofsignalingpathwaysleadingtoincreasedproductionofECMproteinsandcellular dysfunction/death.ChronicdiabetesleadstotheactivationofanumberofsignalingproteinsincludingproteinkinaseC,pro- teinkinaseB,andmitogen-activatedproteinkinases.Thesesignalingcascadesareactivatedinresponsetohyperglycemia-induced oxidativestress,polyolpathway,andadvancedglycationendproductformationamongothers.Theaberrantsignalingpathways ultimatelyleadtoactivationoftranscriptionfactorssuchasnuclearfactor-κBandactivatingprotein-1.Theactivityofthesetran- scriptionfactorsisalsoregulatedbyepigeneticmechanismsthroughtranscriptionalcoactivatorp300.Thesecomplexsignaling pathwaysmaybeinvolvedinglucose-inducedalterationsofendothelialcellphenotypeleadingtotheproductionofincreased ECMproteinsandvasoactivee?ectormoleculescausingfunctionalandstructuralchangesinthemicrovasculature.Understand- ingofsuchmechanisticpathwayswillhelptodevelopfutureadjuvanttherapiesfordiabeticretinopathy. Copyright?2007Z.A.KhanandS.Chakrabarti. This is an open access article distributed under the Creative Commons AttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkis properlycited. 1. INTRODUCTION theretinadevelops.Thedevastatingoutcomeoftheprolif- erativeretinopathyishemorrhageandtractionalretinalde- tachment. Diabeticretinopathy(DR),themostcommoncauseofblind- ness in the working population, is also the m