Furthermore, our study is focused on the regulation of ceramide de novo biosynthesis enzyme SPT; contributions of other products of SPT pathway, besides ceramide, and the role of other ceramide generation pathways including sphingomyelinase and salvage pathways41, in the activation of Rac1–Nox2 signaling in diabetic retinopathy cannot be ruled out. This evidence concerns the gene RAC1 and diabetic retinopathy.