Functional Implication of Dp71 in Osmoregulation and Vascular Permeability of the Retina 英文参考文献.docVIP

FunctionalImplicationofDp71inOsmoregulationand VascularPermeabilityoftheRetina AbdoulayeSene1,2,RaminTadayoni1,2,ThomasPannicke3,AntjeWurm3,BrahimElMathari1,2 ,Romain Benard1,2,MichelJosephRoux4,DavidYaffe5,DominiqueMornet6,AndreasReichenbach3 ,Jose-Alain Sahel1,2,7,AlvaroRendon1,2 * 1InstitutNationaldelaSante etdelaRechercheMe′dicale, UMR_S968,InstitutdelaVision,Paris,France, 2Universite′ Pierreet MarieCurie-Paris6,UMR_S968,Paris, France,3PaulFlechsigInstituteofBrainResearch,Universita¨t Leipzig,Leipzig,Germany,4InstitutdeBiologieMole′culaireetCellulaire,DepartmentofNeurobiologyand Genetics,CNRSUMR7104,Universite′ deStrasbourg,Illkirch, France, 5Department ofMolecular CellBiology,Weizmann Institute ofScience, Rehovot, Israel, 6Institut National de la Sante et de la Recherche Me′dicale, ERI 25 ‘‘Muscle et Pathologies’’, Universite′ Montpellier 1, EA 4202, CHU Arnaud de Villeneuve, Montpellier, France, 7CentreHospitalierNationald’Ophtalmologiedesquinze-vingts,Paris,France Abstract Functional alterations of Mu¨ller cells, the principal glia of the retina, are an early hallmark of most retina diseases and contribute to their further progression. The molecular mechanisms of these reactive Mu¨ller cell alterations, resulting in disturbed retinal homeostasis, remain largely unknown. Here we show that experimental detachment of mouse retina induces mislocation of the inwardly rectifying potassium channels (Kir4.1) and a downregulation of the water channel protein (AQP4) in Mu¨ller cells. These alterations are associated with a strong decrease of Dp71, a cytoskeleton protein responsibleforthelocalizationandtheclusteringofKir4.1andAQP4.Partial(indetachedretinas)ortotaldepletionofDp71 in Mu¨ller cells (in Dp71-null mice) impairs the capability of volume regulation of Mu¨ller cells under osmotic stress. The abnormal swelling of Mu¨ller cells In Dp71-null mice involves the action of inflammatory mediators. Moreover, we investigated whether the alterations in Mu¨