Leukocytes regulate retinal capillary degeneration in the diabetic mouse via generation of leukotrienes

[摘要] UnderstandingtheearlypathogenesisofDRmayuncovernewtherapeutictargetstopreventorslowtheprogressionofthissight‐threateningdisorder.Weinvestigatedtheroleofleukocyte‐mediatedgenerationofLTsinregulationofretinalcapillarydegenerationandinflammationinthediabeticmouse.Wegenerated(1)chimericmicethatlackedtheabilitytogenerateLTsbytransplanting5LO−/−bonemarrowcellsintoND.WTmiceandintoSD.WTmiceand(2)“control”chimericmicebytransplantingWTbonemarrowcellsinto5LO−/−miceorintoWTmice.RetinasfromdiabeticchimericmicewithWTmarrowdemonstratedcapillarydegenerationtothesameextentasretinasfromdiabetic,nonchimericWTmice.Incontrast,retinasfromdiabeticchimericmicewith5LO−/−marrowdevelopedsignificantlylesscapillarydegenerationandpericyteloss(P<0.05).IntheretinasfromchimericmicewithWTmarrow,diabetesinducedariseinleukocyteadherencetothemicrovasculature,expressionoftheNF‐κBp65subunit,andICAM1,superoxidegeneration,andretinalmicrovascularpermeability,yetthesecharacteristicresponseswerebluntedby>50%indiabeticchimerascontaining5LO−/−leukocytes(P<0.05).OurdatasuggestthecriticalinvolvementofleukocytesandLTsintheregulationofinflammationandcapillarydegenerationinDR...

[学科分类] 生理学

[关键词] 5‐lipoxygenase;inflammation;transcellular synthesis