机构：[1]Cent South Univ, Dept Ophthalmol, Xiangya Hosp 2, Changsha, Peoples R China[2]Hunan Clin Res Ctr Ophthalm Dis, Changsha, Peoples R China[3]Chinese Peoples Liberat Army Med Sch, Beijing, Peoples R China[4]Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China[5]Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Hunan, Peoples R China[6]139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China
Glaucoma, one of the most common ocular neurodegenerative diseases worldwide, is characterized by retinal ganglion cell (RGC) loss. There is a large body of literature that describes the neuroprotective role of melatonin against neurodegenerative diseases by regulating neuroinflammation, although the exact mechanism through which melatonin acts on RGC is still uncertain. This study assessed the protective effects of melatonin using a NMDA-induced RGC injury model, and studied the possible mechanisms involved in this process. Melatonin promoted RGC survival, improved retinal function, and inhibited the apoptosis and necrosis of retinal cells. To understand the mechanism of the neuroprotective effects of melatonin on RGC, microglia and inflammation -related pathways were assessed after melatonin administration and microglia ablation. Melatonin promoted RGC survival by suppressing microglia-derived proinflammatory cytokines, in particular TNF alpha, which in turn inhibited the activation of p38 MAPK pathway. Inhibiting TNF alpha or manipulating p38 MAPK pathway protected damaged RGC. Our results suggest that melatonin protects against NMDA-induced RGC injury by inhibiting the microglial TNF alpha-RGC p38 MAPK pathway. It should be considered a candidate neuroprotective therapy against retinal neurodegenerative diseases.
基金：
National Natural Science Foundation of China [82070967, 81770930, 81700837]; Hunan Pro- vincial Innovation Foundation For Postgraduate [CX20210115]; Fundamental Research Funds for the Central Universities of Central South University [2021zzts0358]
第一作者机构：[1]Cent South Univ, Dept Ophthalmol, Xiangya Hosp 2, Changsha, Peoples R China[2]Hunan Clin Res Ctr Ophthalm Dis, Changsha, Peoples R China
通讯作者：
通讯机构：[*1]139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China[6]139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China
推荐引用方式(GB/T 7714)：
Zou Jingling,Yang Jia,Chen Biyue,et al.Melatonin protects against NMDA-induced retinal ganglion cell injury by regulating the microglia-TNF?-RGC p38 MAPK pathway[J].INTERNATIONAL IMMUNOPHARMACOLOGY.2023,118:109976.doi:10.1016/j.intimp.2023.109976.
APA：
Zou, Jingling,Yang, Jia,Chen, Biyue,Jiang, Jikuan,Liu, Jingyuan...&Jiang, Bing.(2023).Melatonin protects against NMDA-induced retinal ganglion cell injury by regulating the microglia-TNF?-RGC p38 MAPK pathway.INTERNATIONAL IMMUNOPHARMACOLOGY,118,
MLA：
Zou, Jingling,et al."Melatonin protects against NMDA-induced retinal ganglion cell injury by regulating the microglia-TNF?-RGC p38 MAPK pathway".INTERNATIONAL IMMUNOPHARMACOLOGY 118.(2023)
医学