Amelioration of experimental autoimmune uveoretinitis by inhibition of glyceraldehyde‐derived advanced glycation end‐product formation

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: diabetic iritis;    EAU;    glycer‐;    AGE;    pyridoxamine;    uveitis;   

DOI  :  10.1189/jlb.3A0513-288RRR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

AGEsarepermanentlymodifiedmacromoleculederivativesthatformthroughnonenzymaticglycationofaminogroupsofproteins.Glycer‐AGEsarehighlytoxicandplayanimportantroleinthepathogenesisofchronicinflammatorydiseases.However,thecontributionofglycer‐AGEstothepathogenesisofuveitisisunclear.Inthisstudy,wemeasuredserumlevelsofglycer‐AGEsin100patientswithendogenousuveitis(22withHLA‐B27‐associateduveitis,20withVKHdisease,14withBehçet'sdisease,and44withsarcoidosis)and33healthyvolunteers.WethenexaminedtheeffectoftheAGEinhibitorinamousemodelofhumanendogenousuveitis(EAU)bycontinuousoraladministrationofpyridoxamineat200or400mg/kg/day.Regardlessoftheetiology,serumglycer‐AGElevelsweresignificantlyhigherinpatientswithuveitisthaninhealthysubjects.Treatmentwith400mg/kgpyridoxaminesignificantlyreducedtheclinicalandhistologicalseverityofEAUandwasaccompaniedbyasignificantdecreaseinserumandretinalglycer‐AGElevelsandsuppressionoftranslocationofNF‐κBp65intothenucleusofretinalcells.Serumglycer‐AGElevelsmaythereforeserveasabiomarkerofhumanuveitis,aswellassystemicinflammation,andmaycontributetotheprogressionofuveitis,includingdiabeticiritis,viatheactivationofNF‐κB...

【 授权许可】

CC BY