Valproate reduces retinal ganglion cell apoptosis in rats after optic nerve crush  

作　　者：Feng Pan Dan Hu Li-Juan Sun Qian Bai Yu-Sheng Wang Xu Hou 

机构地区：[1]Eye Institute of Chinese PLA and Department of Ophthalmology,Xijing Hospital,Fourth Military Medical University,Xi’an,Shaanxi Province,China

出　　处：《Neural Regeneration Research》2023年第7期1607-1612,共6页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.30772368(to DH),81371034(to XH);the Key Project of Natural Science Foundation of Shaanxi Province,No.2017JZ025(to DH).

摘　　要：The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons.

关 键 词：APOPTOSIS C/EBP homologous protein CASPASE-12 endoplasmic reticulum glucose-regulated protein 78 optic nerve crush phosphorylated eukaryotic translation initiation factor 2α retinal ganglion cells unfolded protein response valproate 

分 类 号：R774.6[医药卫生—眼科]