Grape Seed Proanthocyanidins Protect Against Diabetic Retinopathy in Mice

Grape seed proanthocyanidins (GSP), well-known dietary nutrients for public health, have been reported to alleviate diabetic retinopathy, but the underlying mechanisms remain largely unknown. Eight-week-old C57BL/6 mice were used. They were fed a high-fat diet and intraperitoneally injected with 50 mg/kg streptozotocin for five consecutive days to induce diabetes. One week later, 500 mg/kg GSP was given as a dietary supplement for 12 consecutive weeks in diabetic mice. Retinal degeneration, oxidative stress, and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were assessed. GSP significantly reduced body weight and fasting blood glucose in diabetic mice. Diabetic retinopathy-impaired thickness of retina was also increased by GSP supplementation. Moreover, the expressions of vascular endothelial growth factor and glial fibrillary acidic protein induced by diabetic retinopathy were remarkably reduced by GSP. Furthermore, diabetic retinopathy-provoked oxidative stress, including over-production of reactive oxygen species and malondialdehyde, and attenuated activities of superoxide dismutase and catalase were all restored by GSP. Additionally, GSP also activated the Nrf2 signaling pathway, which was inhibited by diabetic retinopathy. These findings demonstrate that GSP ameliorates diabetic retinopathy by reducing oxidative stress, in which the Nrf2 signaling pathway is likely involved. This suggests that GSP might serve as a potential retina-protective candidate for diabetic retinopathy.