Furthermore, data from both in vitro (human retinal endothelial cells in culture) and in vivo models (retinal microvasculature from streptozotocin-induced diabetic rats) models of diabetic retinopathy have shown that homocysteine supplementation further exacerbates hyperglycemia-induced activation of DNA methyl transferases (Dnmts), and hypermethylation of DNA at the promoter of Timp1, facilitating MMP-9-activated mitochondrial damage (unpublished data). This evidence concerns the gene MMP9 and diabetic retinopathy.