A Novel Therapeutic Strategy for Diabetic Retinopathy by Using the Dual PARP-VEGFR Inhibitor

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Diabetic retinopathy (DR) is one of the most common complications of diabetes. The current gold standard for treating DR involves using anti-VEGF antibodies to inhibit angiogenesis in late-stage proliferative diabetic retinopathy. However, this approach often results in recurrence and numerous complications, emphasizing the need for new treatment options. Recent findings suggest that VEGF inhibitors might inadvertently cause vascular damage, diminishing efficacy and potentially accelerating disease progression. In contrast, vascular endothelial growth factor receptor inhibitors (VEGFRi) can simultaneously block the activation of both embedded and soluble VEGFR, offering more significant therapeutic potential. Poly (ADP-ribose) polymerase (PARP), a nuclear enzyme involved in the cellular response to DNA damage, is activated in the early stages of DR. Inhibiting PARP can effectively alleviate DR progression, making it a viable therapeutic target. These insights underpin the potential of a combined VEGFRi and PARPi approach for DR treatment. We used bEnd3 cells, exposing them to media with varying glucose concentrations under normoxic and hypoxic conditions. The expressions of PARP, VEGFR were evaluated under these conditions. Our research demonstrated significant upregulation of PARP and VEGFR3 in the endothelial cells of individuals with DR, underscoring their importance in disease progression. In conclusion, the dual inhibition of PARP and VEGFR3 presents as a novel and promising therapeutic approach for DR. However, further studies are required to determine the efficacy of this strategy conclusively.