EXPRESSION OF NEUROFILAMENTS IN THE RETINA IN EXPERIMENTAL DIABETIC RETINOPATHY AND THE INFLUENCE OF THE BENZODIAZEPINE RECEPTOR AGONIST CARBACETAM

Abstract

Background. One of the typical neurochemical pathogenetic mechanisms causing the dysfunction of retinal neurons in diabetic retinopathy (DR) is a deficiency of GABA-ergic mediation. To some extent, this justifies the prospect of using GABA receptor modulators, including benzodiazepines. Aim: To determine the expression of neurofilaments in the initial stages of the experimental DR development and the influence of the benzodiazepine receptor agonist Carbacetam. Materials and methods. DR was modeled in 35 three-month-old male Wistar rats by a single injection of streptozotocin (50 mg/kg; Sigma-Aldrich, Co, China). The rats were divided into 3 groups: control, with the introduction of Insulin (30 Units; Novo Nordisk A/S, Bagsvaerd, Denmark) and with the introduction of Insulin and Carbacetam (5 mg/kg). NF-H neurofilaments (ThermoFisher Scietific, USA) were detected in the retina by immunohistochemistry. Results. Before DR modeling, NF-H-positive staining was detected in the inner and outer layers of the retina in mainly longitudinal fibers of different lengths, which corresponded to the axons of horizontal and amacrine cells; as well as in fibers and axonal hills of ganglion neurons. In the dynamics of the DR development in the plexiform layers of the retina, a progressive decrease in the intensity of staining was observed. In the optic fiber layer, staining was concentrated around dilated microvessels that tended to form microaneurysms. On the 28th day, NF-H-positive staining disappeared in the inner plexiform layer. Administration of Insulin with Carbacetam prevented the loss of NF-H-positive staining in the layers of the retina. Conclusion. The use of the benzodiazepine receptor agonist Carbacetam may be a promising direction for the correction of retinal neurodegeneration in DR.