Role of cytokines, neuropeptids and matrix metalloproteinases in the immunopathogenesis of retinal neurodegeneration in diabetic retinopathy

Currently, diabetic retinopathy (DR) is considered both a vascular lesion, as well as a neurodegenerative disease. The normal functioning of the glia and retinal neurons depends on the balance between the cytokine system, neurotrophic factors and matrix metalloproteinases. The disorders that occur in these systems are assigned an important role in many neurodegenerative processes. The purpose of the present study was to determine the levels of IL-1β, IL-17A, TNFα, IFNγ, IL-10, TGF-β1, TGF-β2, TGF-β3, MMP- 2, MMP-7, MMP-9, TIMP-1, TIMP-2, S100b protein, BDNF and NGF in the serum of patients with type 2 diabetes mellitus with signs of retinal neurodegeneration, and to identify additional immunological markers for diagnosis and prediction of their clinical course. The study included 80 patients with endocrinogically verified diagnosis of type 2 diabetes. All subjects were examined at an optical coherent tomograph RTVue-100 (USA), and the volume of focal loss of retinal ganglion cells (FLV) was determined. According to its results, the patients of the main group were divided into 2 subgroups. The first group included 22 persons in whom the FLV indexes did not show significant differences from the controls. The second group included 58 patients with a significantly larger FLV volume. In the subgroup of patients with high level of focal GCS loss, a significant increase in the level of IL-1β and IL-10 deficiency was revealed in comparison with the controls, and the subgroup without significant losses of GCS over the entire observation period. TGF-β3 deficiency was found in patients of subgroup 2 versus controls and subgroup 1. An imbalance in the tissue proteolysis system was revealed, MMP-9 and TIMP-2 levels were elevated, and MMP-7 levels were decreased in both subgroups compared to controls. When analyzing serum contents of neurospecific proteins in the group of patients with OCT signs of retinal neurodegeneration, high levels of the S100b protein and NGF were revealed, in contrast to the control group and subgroup 1.