More importantly, since the activation of p38 MAP kinase is demonstrable at a time point (3 hours), much earlier than the onset of mitochondrial dysfunction [4, 5], these data suggest that Nox2 signaling pathway-mediated increase in stress kinase activation triggers mitochondrial dysfunction and apoptosis of endothelial cells leading to diabetic retinopathy. This evidence concerns the gene CYBB and diabetic retinopathy.