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Aims Hypoglycemia is associated with increased reactive oxygen species (ROS) production and vascular events. We have previously reported that low-glucose (LG) conditions induce mitochondrial ROS (mtROS) production in aortic endothelial cells (ECs). However, the mechanism by which hypoglycemia promotes diabetic retinopathy (DR) is unclear. Blood-retinal barrier (BR disruption occurs in the early stages of DR. We hypothesized that the mechanisms underlying hypoglycemia-induced DR are associated with BRB breakdown due to mtROS generation