Diabetic Neovascularization Defects in the Retina Are Improved by Genistein Supplementation in the Ovariectomized Rat

Genistein seems to have a protective and therapeutic effect on conditions associated with neovascular growth in the retina. This study investigated the angiogenesis, antioxidant, and anti-inflammatory effect of genistein on the retinas in ovariectomized diabetic rats. In this study, 40 female albino Wistar rats were divided into four groups (n = 8 per group): sham, ovariectomized group (OVX), OVX + diabetes (OVX.D), and OVX.D + genistein (OVX.D.G). OVX induced by removal of bilateral ovaries and then high-fat diet (HFD) and a low dose of streptozotocin (STZ) (1 mg/kg; intraperitoneal (IP) injection) was used for diabetes induction (OVX.D) with 8 weeks of genistein treatment (OVX.D.G). At the end of 8 weeks, the retina was removed under anesthesia. The samples were used to measure extracellular signal-regulated kinase (ERK), matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF), and nuclear factor NF-kappa-B (NF-κB) by western blotting and inflammatory factors ELISA and oxidative stress. Measurements of glutathione (GSH) and malondialdehyde (MDA) showed that OVX and especially OVX.D significantly decreased GSH and increased MDA level in the retina, but genistein reversed these effects in OVX.D.G groups. Also, OVX and OVX.D significantly increased VEGF, MMP-2, p-ERK, NF-κB, interleukin-1beta (IL-1β), and tumor necrosis factor alpha (TNFα) expression in the retina of OVX and OVX.D groups in comparison to the sham group (p < 0.05). However, a significant reduction of these proteins was observed in the genistein-treated group (p < 0.05). In conclusion, bilateral ovariectomy and subsequently estrogen deficiency caused the development of inflammation, neovascularization, and then retinopathy in STZ-induced diabetic ovariectomized rats. On the basis of the results, genistein administration may be a practical approach for improving symptoms and complications of ovariectomized diabetic retinopathy.