Over-activated canonical Wnt signaling in DR and potential therapeutic inhibitors of canonical Wnt signaling for DR. In diabetic conditions, hyperglycemia induces the up-regulation of Wnt signaling in the retina. Levels of Wnt signaling components, low-density lipoprotein receptor-related protein 6 (LRP6), Frizzled 7 and β-catenin are up-regulated, and the Wnt signaling downstream target genes are over-expressed, which results in angiogenesis, inflammation and increased oxidative stress in diabetic retina and leads to DR. Wnt signaling inhibitors with therapeutic potential – SERPINA3K: Serine proteinase inhibitors 3K, PEDF: Pigment epithelium-derived factor, VLDLR: very low-density lipoprotein receptor, DKK1: dickkopf-related protein 1. Mab2F1: an anti-LRP6 monoclonal antibody which was generated in our laboratory.