Microglia disulfidptosis contributes to worsening of diabetic retinopathy induced by acute hypoglycemia

This study examines a critical safety concern in diabetes treatment: why rapid improvement in blood sugar control can sometimes temporarily exacerbate diabetic retinopathy. We explore the role of acute hypoglycemia (low blood sugar) in triggering a novel form of cell death called disulfidptosis in retinal immune cells (microglia). Our findings demonstrate that glucose deprivation initiates a destructive chain reaction in microglia, driven by the SLC7A11 protein, which leads to severe oxidative stress and activation of the Rac1-WRC pathway, causing cytoskeletal collapse and inflammatory cell death. The research identifies disulfidptosis of microglia as a potential therapeutic target for this hypoglycemia-induced complication, offering new strategies to make intensive diabetes management safer for the retina.