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Danyang Chen, Erica Little; A Wnt Inhibitor for Treatment of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1941.
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Diabetic retinopathy is characterized by multiple pathological processes which are associated with numerous molecular pathways, such as vascular endothelial growth factor, Wnt, inflammation and other pathways. Accumulated evidence has demonstrated that the Wnt pathway is responsible for diabetic retinopathy. Thus, the drugs targeting Wnt pathway would be effective in the treatment of diabetic retinopathy.
The effects of a Wnt inhibitor (CLT-010) on the Wnt pathway and retinal vascular endothelial cell growth were determined. Dual-luciferase reporter assay and Western blotting were performed to evaluate the effects of CLT-010 on the Wnt signaling activation and Wnt-responsive gene expression, respectively. MTT assay was used to examine the cell viability.
CLT-010 attenuated the Wnt pathway over-activation by affecting the phosphorylation of low-density lipoprotein receptor-related protein 6 and β-catenin. The compound also down-regulated Wnt3a-induced over-expression of Wnt-responsive gene and inhibited the growth of retinal vascular endothelial cells.
CLT-010 had inhibitory effects on the over-activation of Wnt signaling, over-expression of Wnt-responsive gene and growth of retinal vascular endothelial cells.
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