Hua Wang Y, Wu Wang D, Qin Yin Z
Department of Ophthalmology, General Hospital of Chinese People's Liberation Army, 100853 Beijing, People's Republic of China; Taiyuan Aier Eye Hospital, Aier Eye Hospital Group, 030000 Taiyuan, People's Republic of China.
Taiyuan Aier Eye Hospital, Aier Eye Hospital Group, 030000 Taiyuan, People's Republic of China.
J Fr Ophtalmol. 2020 Oct;43(8):718-726. doi: 10.1016/j.jfo.2020.02.003. Epub 2020 Jul 4.
Our recent in vivo studies have shown that olfactory ensheathing cells (OECs) and α-crystallin can promote retinal ganglion cell (RGC) survival and axonal regeneration synergistically after optic nerve injury. However, the mechanism is still unknown.
Here, we studied the synergistic effect and mechanism of OECs and α-crystallin on RGC survival after HO-induced oxidative damage and a crushing injury to the optic nerve in an adult rat model.
After HO-induced oxidative damage, RGC-5 cells were treated with OECs, α-crystallin or a combination of OECs and α-crystallin. Apoptosis of RGC-5 cells was assessed by flow cytometry. Phosphorylated Akt, BAD, and cleaved-caspase3 were detected by Western blot after optic nerve injury in vivo and HO-induced RGC-5 oxidative damage in vitro.
The results showed that OECs and α-crystallin could both independently inhibit RGC-5 apoptosis (P<0.01), increase the phosphorylation of both Akt and BAD, and decrease the activation of caspase-3 (P<0.01). However, the effect of the combination of both was more significant than either alone.
These findings indicate that inhibition of superoxide damage to RGCs through regulation of the Akt/BAD pathway is one of the mechanisms by which OECs and α-crystallin promote optic nerve recovery after injury.
我们最近的体内研究表明，嗅鞘细胞（OECs）和α-晶体蛋白在视神经损伤后可协同促进视网膜神经节细胞（RGC）的存活和轴突再生。然而，其机制仍不清楚。
在此，我们在成年大鼠模型中研究了OECs和α-晶体蛋白对HO诱导的氧化损伤及视神经挤压伤后RGC存活的协同作用及其机制。
HO诱导氧化损伤后，用OECs、α-晶体蛋白或OECs与α-晶体蛋白的组合处理RGC-5细胞。通过流式细胞术评估RGC-5细胞的凋亡情况。在体内视神经损伤和体外HO诱导的RGC-5氧化损伤后，通过蛋白质免疫印迹法检测磷酸化的Akt、BAD和裂解的caspase3。
结果显示，OECs和α-晶体蛋白均可独立抑制RGC-5凋亡（P<0.01），增加Akt和BAD的磷酸化，并降低caspase-3的激活（P<0.01）。然而，两者组合的效果比单独使用任何一种更显著。
这些发现表明，通过调节Akt/BAD途径抑制超氧化物对RGCs的损伤是OECs和α-晶体蛋白促进损伤后视神经恢复的机制之一。
