The Influence of Tyrosine Protein Kinases Blockade on the Vasculonedothelial Growth Factor Expression and Diabetic Retinopathy Development

Abstract

One of the main factors in the development of diabetic retinopathy (DR) is vasculoendothelial growth factor (VEGF), which is the end product of the activation of several intracellular signaling pathways, including those triggered by the activation of receptor tyrosine protein kinases. There is a need to justify new approaches to influence the expression of VEGF, not only in the late but also in the early stages of DR. Diabetes was modeled in 45 three-month-old male Wistar rats by a single injection of streptozotocin (50 mg/kg; Sigma- Aldrich, China). Hyperglycemia led to the development of early (on the 7–28th day) morphological manifestations of DR, indicating pronounced degenerative changes in nerve cells, microcirculation, and metabolism disorders. The use of insulin resulted in fewer diabetic changes in the retina, while the combined use of insulin and the tyrosine protein kinase blocker imatinib prevented the morphological manifestations of DR. According to the results of an immunohistochemical study, overexpression of VEGF was observed in the retinal tissue, which was inhibited by the introduction of insulin and, to a greater extent, by the combination of insulin with imatinib. According to immunoblotting results, the levels of VEGF and hypoxia-inducible factor (HIF-1) in the retinal tissue increased several-fold, which was significantly inhibited by insulin and prevented by insulin in combination with imatinib. Thus, this suggests that blockade of tyrosine protein kinases may be a highly effective way of preventing or correcting the damage caused by DR.