Effect of cellular protein kinases blockade on the s100 retina expression in experimental diabetic retinopathy

The positive effect of cellular protein kinases blockade in diabetes and diabetic retinopathy (DR) justifies the need to clarify molecular mechanisms, among which the trigger regulatory role belongs to calcium-binding proteins S100. Aim: to establish the expression of S100 protein in retinal tissues and the effect of cellular protein kinases blockade with Sorafenib on it in experimental DR. Materials and methods. Diabetic retinopathy was modeled in male Wistar rats. For this purpose, they were administered a single injection of streptozotocin at a dose of 50 mg/kg (Sigma-Aldrich, Co, China). Experimental rats were divided into three groups: control; with the administration of insulin 30 U (NovoNordiskA/S, Bagsvaerd, Germany); with the administration of insulin and sorafenib at a dose of 50 mg/kg (Cipla, India). Monoclonal antibodies against S100 (ThermoFisher Scietific, USA) were used during immunohistochemical studies. Results. With the development of experimental DR, the expression of S100 protein significantly increased in the bodies and processes of astrocytes and Müller cells. The latter were mainly located in the inner nuclear layer, significantly increased in size and had a process-like shape (reactive gliosis). Intensely stained S100-positive astrocyte fibers were in close contact with microaneurysms that formed on the retina inner surface. The appearance of individual S100-positive cells in the outer layers of the retina was noted. Treatment of animals with insulin led to a decrease in the expression of the S100 protein, and the use of Sorafenib prevented the activation of the expression of the S100 protein, preventing the development of DR, reactive gliosis, and the formation of microaneurysms on the inner surface of the retina. Conclusions. One of the mechanisms of the positive effect of Sorafenib in DR was discovered – the prevention of reactive gliosis, which prevented early manifestations of DR.