Curcumin inhibits ferroptosis-mediated vascular occlusion by regulating the CXCL10/CXCR3 axis in retinopathy of prematurity.

Abstract

Retinopathy of prematurity (ROP) is a disorder that causes blindness in children at a high incidence. Retinal endothelial cells are damaged by variations in oxygen partial pressure, which leads to vascular obstruction and, eventually, ischemia and hypoxia, which cause the formation of new blood vessels. However, little is known about the molecular mechanism of hyperoxic vascular occlusion. High oxygen levels are thought to cause ferroptosis. In this study, experiments with both animal and in vitro models demonstrated that elevated expression of C-X-C motif chemokine ligand 10 (CXCL10)/C-X-C motif chemokine receptor 3 (CXCR3) in retinal vascular endothelial cells induced ferroptosis. Curcumin decreased ferroptosis by inhibiting the production of CXCL10/CXCR3. Curcumin also preserved distal sprouts and filopodia, increasing tip cell and astrocyte counts. As a result, we hypothesize that curcumin reduces ferroptosis and preserves retinal blood vessels under hyperoxic conditions by suppressing the CXCL10/CXCR3 axis. Coimmunoprecipitation (COIP) data were used to determine which proteins interact with CXCR3 during ferroptosis. For the first time, our study applied curcumin to treat eye diseases in oxygen-induced retinopathy (OIR) mice and explored the underlying mechanism in cell experiments, laying the foundation for clinical patients to use this drug. Exploring the interaction between CXCL10/CXCR3 and ferroptosis provides an experimental basis for using the CXCL10/CXCR3 axis as a therapeutic target for the treatment of ROP ophthalmopathy.