In summary (Fig. 6), here we report that the hypoxia-induced reduction in EPAC-1 expression and activity contributes to the generation of retinopathy through the disruption of the endothelial barrier in the OIR model, or by eNOS uncoupling (disturbing the NO/ROS balance) in the Ins2Akita model. This evidence concerns the gene NOS3 and retinal disorder.