Therapeutic Potential of a Monoclonal Antibody Blocking the Wnt Pathway in Diabetic Retinopathy

Dysregulation of Wnt/b-catenin signaling contributes to the devel-opment of diabetic retinopathy by inducing retinal inflammation, vascular leakage, and neovascularization. Here, we evaluated the inhibitory effect of a monoclonal antibody (Mab) specific for the E1E2 domain of Wnt coreceptor low-density lipoprotein receptor–related protein 6, Mab2F1, on canonical Wnt signaling and its therapeutic potential for diabetic retinopathy. Mab2F1 displayed robust inhibition on Wnt signaling with an half-maximal inhibitory concentration (IC50) of 20 mg/mL in retinal pigment ep-ithelial cells. In addition, Mab2F1 also attenuated the accumu-lation of b-catenin and overexpression of vascular endothelial growth factor, intercellular adhesion molecule-1, and tumor necrosis factor-a induced by high-glucose medium in retinal endothelial cells. In vivo, an intravitreal injection of Mab2F1 significantly reduced retinal vascular leakage and decreased pre