Hyperglycemia-Induced Translational Control of Gene Expression in the Retina

Project: Research project

Project Details


The principle evidenced based treatment for proliferative diabetic retinopathy involves laser-mediated ablation, which fails to alter the molecular pathology of the disease, and as such, nearly half of patients require future treatments. The overall goal of this research is to identify new targets for intervention at the molecular level that will lead to development of innovative, nondestructive therapies that target the etiology of diabetic retinopathy. The pathogenesis of this disease is caused by a combination of hyperglycemia and a reduction in insulin mediated signaling, which results in neurovascular complications through the induction of structural and physiological changes in the retina. The research proposed in this application is innovative, because it represents an entirely different approach to address the molecular basis of diabetic retinopathy. The central hypothesis is that the covalent addition of O-linked N-Acetylglucosamine (O-GlcNAcylation) to serine or threonine residues of translation initiation factors mediates a shift from cap-dependent to cap-independent mRNA translation, resulting in an altered gene expression pattern that contributes to the pathophysiology of diabetic retinopathy. With respect to specific outcomes, this research is expected to characterize a novel mechanism that links the metabolic abnormalities associated with diabetes to enhanced vascular growth factor expression in the retina. The rationale is that once the mechanisms underlying altered gene expression in the retina are known, the function/assembly of translation initiation factors can be manipulated pharmacologically, resulting in therapies that address the prevention and treatment of neurovascular complications that produce 24,000 new cases of diabetes related vision loss each year.
Effective start/end date1/1/1412/31/20


  • American Diabetes Association


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