阻断DLK/MKK4/JNK/c-JUN通路对ITON小鼠视网膜神经节细胞存活的影响

doi:10.13418/j.issn.1001-165x.2022.2.12

Abstract

Abstract: Objective　To investigate whether blocking the DLK/MKK4/JNK/c-JUN pathway can promote the survival of retinal ganglion cells (RGCs) in mice with indirect traumatic optic neuropathy (ITON) and compare the blocking effects of different sites.　Methods　6-8 weeks old mice were treated with the impact acceleration (IA) model capable of generating traumatic axonal injury (TAI) to simulate indirect traumatic optic neuropathy (ITON), then eligible mice were screened out and divided into four groups: a sham-operation group, an IA group, an IA+sunitinib group and an IA+SP600125 group. Samples collected at different times of the experiment were detected by γ-synuclein or p-c-JUN immunofluorescence staining, TUNEL staining and Western blot, and the results were statistically analyzed. Results Immunofluorescence staining results showed that compared with IA group, the survival RGCs density of IA+sunitinib group and IA+SP600125 group increased significantly, while the density of p-c-JUN (+) RGCs decreased remarkably (P<0.05). TUNEL test results showed that compared with IA group, the apoptosis RGCs density in both IA+sunitinib group and IA+SP600125 group reduced dramatically (P<0.05). Western blot results showed that compared with the IA group, the expression of corresponding downstream proteins in the DLK/MKK4/JNK/c-JUN pathway in IA+ sunitinib group and IA+SP600125 group decreased noticeably (P<0.05).　Conclusions　The activation of the DLK/MKK4/JNK/ C-JUN pathway is related to the survival rate of RGCs in ITON mice. The application of DLK inhibitors or JNK inhibitors can effectively block the expression of the pathway and promote the survival of RGC, with the latter blocking method having a better effect.

Key words: , Indirect traumatic optic neuropathy, 　DLK, 　JNK, 　Retinal ganglion cells

CLC Number:

R774.1

Chu Xiaoqi, Wu Zheng, Fan Liting, Tao Chunmei, Ma Yue, Ge Yusong. Effect of blocking the DLK/MKK4/JNK/c-JUN pathway on survival of retinal ganglion cells in ITON mice[J]. Chinese Journal of Clinical Anatomy, 2022, 40(2): 181-186.

References 14

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Effect of blocking the DLK/MKK4/JNK/c-JUN pathway on survival of retinal ganglion cells in ITON mice

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