早产儿视网膜病变
视网膜
医学
氧化应激
血管生成
新生血管
血管内皮生长因子
视网膜
眼科
血管内皮生长因子受体
内科学
生物
神经科学
遗传学
胎龄
怀孕
作者
Jianhui Wang,Qi Zhang,Enguang Chen,Peiquan Zhao,Yu Xu
标识
DOI:10.1096/fj.202101785rrr
摘要
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness associated with retinal vaso-obliteration in phase 1 and pathological neovascularization (NV) in phase 2; however, effective and safe treatments for ROP definitive treatment are yet to be determined. Anti-vascular endothelial growth factor (VEGF) therapy mainly focuses on reducing abnormal NV in phase 2 but with high risks of late recurrence and systemic side effects. Previous studies have established that the severity of vaso-obliteration in phase 1 largely influences subsequent stages, suggesting that prevention of vessels loss may be a potential therapeutic target for ROP. Herein, the therapeutic potential and safety of early Elabela intervention treatment in treating phase 1 ROP and the possible underlying mechanisms were investigated using an oxygen-induced retinopathy (OIR) mouse model. It was observed that intraperitoneal injection of Elabela remarkably reduced the avascular retinal area and increased the vascular density in phase 1 of OIR mice. Further investigation revealed that mitochondrion-dependent ferroptosis was involved in oxidative stress-mediated vascular protection loss in phase 1 OIR. Furthermore, we demonstrated that Elabela could rescue mitochondria-dependent ferroptosis via mediating the xCT/GPX4 axis. Collectively, our study revealed that ferroptosis may play a significant role in early ROP, while Elabela may be a safe and promising strategy for the early intervention of ROP.
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