Inhibiting O-GlcNAcylation of YAP for diabetic retinopathy

Inhibiting post-translational O-GlcNAcylation of the transcriptional co-regulators YAP and TAZ in retinal endothelial cells could help treat diabetic retinopathy by promoting phosphorylation and subsequent ubiquitination and degradation of YAP, thus decreasing expression of genes that drive pathogenic endothelial cell activation and angiogenesis in the retinal vasculature.

Levels of UDP-GlcNAc, a sugar molecule that acts as a donor for O-GlcNAcylation, and of YAP and TAZ proteins, were higher in the vitreous fluid and retinal endothelial cells, respectively, from proliferative diabetic retinopathy patients than from ophthalmic disease patients without proliferative diabetic retinopathy. ...