Sirman Y. Pathogenesis of diabetic retinopathy and justification of ways of its correction (experimental research)

The thesis summarizes and proposes a new solution to the current scientific problem of the complications pathogenesis of experimental streptozotocin diabetes, in particular diabetic retinopathy and vascular endothelium dysfunction and their correction. A comprehensive assessment of the development of endothelial dysfunction in experimental diabetic retinopathy was provided and the method of its correction was substantiated. The expediency of the selected biochemical indicators as markers of the severity of the studied pathology was confirmed experimentally. It was established a weakening of the vasodilation process against the background of the development of experimental diabetic, as evidenced by a decrease in the content of S-nitrosothiols. It was shown that in the pathogenesis of streptozotocin diabetic retinopathy, the vasoconstrictor potential of blood vessels significantly increases, as evidenced by a significant increase in endothelin-1 in animals. It has been proven that the development of experimental diabetic retinopathy negatively affects the functional state of blood vessels at each of the stages of the study. The significant changes in the level of Willebrand factor and asymmetric dimethylarginine as markers of endothelial dysfunction in the dynamics of the development of the pathological process were revealed. A study of the pathways of nitric oxide synthesis in experimental diabetic retinopathy and the role of inducible NO synthase in this process was conducted. The development of hypoxia was analyzed based on the dynamics of the level of erythrocytes’ 2,3-diphosphoglycerate in the blood of rats with simulation of diabetic retinopathy. It was determined the imbalance between the pro- and antioxidant system under the conditions of the experimental streptozotocin diabetic retinopathy development. The dynamics and role of the vascular growth factor were investigated to determine the degree of severity of the simulated pathological process. The role of pro- and anti-inflammatory interleukins in the development of endothelial dysfunction in streptozotocin diabetic retinopathy has been proven. A pathogenetically justified method of correction was proposed, where the optimal combination of metformin, aflibercept, L-arginine solution and citicoline was selected experimentally. A mathematical prognostic model of the development of streptozotocin diabetic retinopathy was developed, which is based on the analysis of biochemical indicators of blood in the early stages of the experiment. It was established the effectiveness of a complex analysis of the level of erythrocyte 2,3-diphosphoglycerate with markers of the functional state of endothelial cells (Willebrand factor and endothelin-1) on the 30th day for predicting the course of the pathological process under study.