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Elevated retinal ephrinB2/EphB2 reverse signaling regulates ...

Elevated retinal ephrinB2/EphB2 reverse signaling regulates GluR2 trafficking in a rat experimental glaucomatous model

作     者:Ling-Dan DONG,Yanying MIAO,Xiao-Han WANG,Xiao-Fang YANG,Zhong-Feng WANG~* Institutes of Brain Science,Institute of Neurobiology and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032,China 

会议名称:《中国神经科学学会第九届全国学术会议暨第五次会员代表大会》

会议日期:2011年

学科分类:1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

关 键 词:glaucoma EphB ephrinB retinal ganglion cell apoptosis GluR2 trafficking 

摘      要:Objective Glaucoma,the second leading cause of blindness,is a neurodegenerative disease that is characterized by optic nerve degeneration resulting from apoptotic death of retinal ganglion cells(RGCs).Although previous work has shown that ephrinB2/EphB2 signaling was upregulated in the optic nerve head of glaucomatous DBA/2J mice,the role of ephrinB/EphB signaling in glaucomatous retina is largely *** the present work, we investigated the possible involvement of ephrinB/EphB signaling in the pathogenesis of RGCs death in a rat chronic ocular hypertension(COH) *** COH model was reproduced by blocking episcleral veins. Immunohistochemistry and Western blot techniques were used to detect the expression of EphBl,EphB2,ephrinBl, ephrinB2,phosphorylated EphB,phosphorylated ephrinB,and GluR2 in the *** staining was employed to detect RGCs *** direct interaction between GluR2 and phosphorylated EphB or phosphorylated ephrinB was detected by co-immunoprecipitation(co-IP) ***(1) In normal retina,EphBl was mainly expressed in GFAP-positive Miiller cells and EphB2 was expressed in the ganglion cell layer(GCL) and the inner nuclear layer (INL),while their ligands ephrinBl and ephrinB2 were expressed in both Miiller cells and neurons in the GCL.(2) In COH retina,the expression of EphBl was remarkably increased in Miiller cells,and the expression of ephrinB2 was increased in the endfeet of Muller cells and in neurons of the GCL,while ephrinBl and EphB2 almost kept unchanged. (3) Although total GluR2 proteins in the retinal extract hardly changed,the GluR2 proteins in the membrane component were significantly decreased in the COH *** intravitreal injection of EphB2-Fc,but not ephrinB2-Fc, induced a significant increase of TUNEL-positive signals in the normal retina,which was similar to the observation in the COH ***,injection of EphB2-Fc intravitreally could mimic the expression change of GluR2 in the COH rats.(4) Altho

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