Elabela promotes the retinal angiogenesis by inhibiting ferroptosis during the vaso‐obliteration phase in mouse oxygen‐induced retinopathy model

Abstract

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.

The research trends of ferroptosis in diabetes: a bibliometric analysis

“…Additionally, other investigations have revealed the efficacy of strategies such as elabela and ferrostatin-1 in alleviating ferroptosis in the retina. These strategies have been validated through numerous cellular and animal experiments, indicating their mode of action via activation of the Cystine/glutamate Antiporter system XC (XC-)-GPX4 axis ( 66 , 67 ). The study conducted by Liraglutide, a widely recognized antihyperglycemic agent, primarily modulates oxidative stress and endoplasmic reticulum stress.…”

Spotlight on iron and ferroptosis: research progress in diabetic retinopathy

“…Of paramount significance is the profound ultrastructural degradation of mitochondria, setting it apart from other forms of cell death. This distinctive signature entails mitochondrial atrophy, a reduction in mitochondrial cristae density, and the perturbation of membrane potential ( 19 , 95 ). The nexus between ferroptosis and mitochondrial dysfunction (MD) assumes a complexion characterized by complexity, multifaceted interactions, and interwoven relationships.…”

“…Wang et al. ( 19 ) detailed their findings, revealing noteworthy increments in ROS, lipid peroxides, MDA levels, and excessive iron accumulation within RMECs subjected to H 2 O 2 and RSL3 treatment. These perturbations were mirrored within RMEC mitochondria, accompanied by a decline in membrane potential (MMP).…”

“…This constellation of changes points unequivocally toward a single outcome: ferroptosis. This culmination is anchored in the context of exacerbated oxidative damage, characterized by diminished SLC7A11 and GPX4 levels and compounded by the pathological buildup of iron ( 19 ). Coincidentally, Shao et al.…”

Elabela: Negative Regulation of Ferroptosis in Trophoblasts via the Ferritinophagy Pathway Implicated in the Pathogenesis of Preeclampsia

“…Although several studies had confirmed that Elabela could reverse disease progression by reducing the extent of ferroptosis, no data were available on PE [25][26][27]. Therefore, in this study, we intended to explore the link between Elabela and ferroptosis during PE and the mechanisms that mediate it.…”