Our data from retinal endothelial cells are strongly supported by results from diabetic mice with hyperhomocysteinemia; mice genetically manipulated to experience elevated homocysteine levels in the retina (Cbs+/− mice), have accelerated and exacerbated mitochondrial damage with increase in ROS, and mtDNA damage at shorter duration of diabetes, compared to hyperglycemic mice without hyperhomocysteinemia (Cbs+/+ mice). This evidence concerns the gene CBS and hyperhomocysteinemia.