Antioxidant combination inhibits angiogenesis in diabetic retinopathy by targeting VEGF/PI3K/AKT signaling

Abstract

Abstract Background: Angiogenesis is one of the main hallmarks of diabetic retinopathy (DR), and antioxidants have shown some therapeutic effects in DR. Objective: To investigate the effect and mechanism of action of antioxidant combination on angiogenesis in the process of DR. Methods: Human retinal microvascular endothelial cells (HRMECs) were exposed to high-glucose (HG) and then treated with antioxidants: N-acetylcysteine (NAC) and/or taurine (TAU). HRMECs were assayed for proliferation, migration, apoptosis, and angiogenic capacity. A rat model of DR was induced using streptozotocin (STZ). HE staining was used to observe the retinal thickness of rats. apoptosis was detected by TUNEL assay. protein expression in VEGF/PI3K/AKT pathway was detected by Western blot. Results: HRMECs showed enhanced cell proliferation and migration and reduced apoptosis after exposure to HG, whereas antioxidant treatment attenuated the survival of HRMECs. In addition, the total retinal thickness of DR model rats was very thin, and antioxidant treatment, especially their combined application, significantly thickened their retinas and greatly reduced the level of apoptosis. western blot assays showed that antioxidants may act by inhibiting the activation of VEGF/PI3K/AKT pathway. Conclusion: Antioxidants may inhibit angiogenesis by inhibiting VEGF/PI3K/AKT signaling, thereby improving the extent of DR.