Epigenetic Modifications and Potential New Treatment Targets in Diabetic Retinopathy

Figure 5

TXNIP: a novel therapeutic target and a novel therapeutic strategy. Hyperglycemia induces TXNIP expression, which leads to oxidative damage that is the major downstream effect of hyperglycemia. Indeed, we demonstrated that TXNIP is responsible for neurovascular dysfunction in DR. We developed a novel gene therapy technique: we injected in the diabetic retina small interfering RNA (siRNA) targeted to TXNIP promoter associated with cell penetrating peptides (CPP) containing a nuclear localization signal. In diabetic conditions, the cotranscriptional factor p300 is associated with TXNIP promoter, leading to enhanced TXNIP expression. When we injected the siRNA targeted to TXNIP promoter, they completely block the recruitment of p300 on TXNIP promoter, inhibiting TXNIP expression. With this technique, we completely blocked the progression of DR.