According to the results of recent studies, diabetic retinopathy can be considered not only as a vascular disease, but also as a neurodegenerative process. Study of the composition of the tear fluid is used to assess the state of local immunity in the development of eye diseases. However, studies examining the effect of tear composition in diabetic retinopathy are few. The aim of the study is to determine the levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100b, BDNF and NGF in the tear fluid ofpatients with vascular and neurodegenerative manifestations of diabetic retinopathy. The study included 80 patients diagnosed with type 2 diabetes which were divided into 2 groups: the 1st group included 40 patients who had no clinical signs of diabetic retinopathy on the fundus; the 2nd group included 40 patients with initial signs of non-proliferative diabetic retinopathy. All those included in the study were examined on an optical coherent tomograph RTVue-100 (USA); the volume of focal losses of retinal ganglion cells (FLV) was determined. An increase in FLV above the normative base of the device was regarded as an OCT-sign of retinal neurodegeneration. According to the results of OCT, the participants of the first and second groups were additionally divided into 4 subgroups: 1A — patients without vascular changes in the fundus and without OCT signs of retinal neurodegeneration (n = 12); 1B — patients without vascular changes in the fundus and with the presence of OCT signs of retinal neurodegeneration (n = 28); 2A — patients with initial non-proliferative DR and without OCT signs of retinal neurodegeneration (n = 10); and 2B — patients with initial non-proliferative DR and with OCT signs of retinal neurodegeneration (n = 30). The levels of IL-1β, IL-10, TGF-β3, MMP-7, TIMP-2, protein S100 b, BDNF, and NGF in tear fluid were determined by enzyme-linked immunosorbent assay. Levels of IL-1β and IL-10 in tear fluid in all subgroups were comparable to controls throughout the study. TGF-β3 content in the tear fluid of patients in the group with initial signs of non-proliferative DR (group 2) was significantly (p = 0.001) lower compared with control and group 2. However, there was no significant difference (p > 0.05) between subgroups A and B within groups. The concentration of MMP-7 in the tear fluid in all subgroups was significantly lower than in the control (p < 0.05). However, in the subgroups with OCT signs of retinal neurodegeneration (1B and 2B), the deficiency of this metalloproteinase was more pronounced (p = 0.0001). The levels of the neuropeptides under study NGF, BDNF and S100 B in tear fluid did not differ from controls in all subgroups.

Objective: To detect early morphological and functional signs of neurodegeneration of the retina in patients with type 2 diabetes mellitus (DM) without signs of diabetic retinopathy (DR), to determine the presence and nature of the relationship between the studied parameters.Methods: The study included 30 patients with type 2 DM without DR (main group) and 30 healthy individuals (control group). Optical coherence tomography and microperimetry were performed.Results: In the main group, a significant decrease in the average photosensitivity of the retina and a decrease in its photosensitivity in the fovea and in the upper, lower, and temporal quadrants of parafovea were revealed. A significant difference between the groups was also recorded in the thickness of the inner layers of the retina in the temporal quadrant of parafovea. There was also a significant difference in the volume of focal loss of retinal ganglion cells.Conclusions: Neurodegenerative and related functional changes in the retina were revealed in patients with type 2 DM without signs of DR. Retinal neurodegeneration is one of the reasons for the deterioration of visual function in patients with DM and can aggravate the prognosis of the disease. Optical coherence tomography and microperimetry can be used for early diagnosis and monitoring of this process.

Цель исследования -определить уровень матриксных металлопротеиназ-2,7,9 (ММП-2,7,9) и их тканевых ингибиторов 1-го и 2-го типов (ТИМП-1, ТИМП-2) в сыворотке крови и слезе у пациентов с сахарным диабетом 2-го типа и оценить взаимосвязь признаками нейродегенерации сетчатки. В основную группу исследования включены 80 пациентов с СД 2-го типа. Пациентам проведены оптическая когерентная томография и микропериметрия. Уровень ММП-2, ММП-7, ММП-9, ТИМП-1, ТИПМ-2 в сыворотке крови и слезе определяли методом иммуноферментного анализа. Зафиксирован дефицит ММП-7 в слезе и сыворотке крови у пациентов с сахарным диабетом 2-го типа. Содержание ММП-9 у пациентов основной группы было выше в обеих биологических жидкостях. Выявлено повышение уровня ТИМП-2 в сыворотке крови у больных СД 2-го типа. Выявлена отрицательная корреляция между уровнем ММП-7 в слезе и объемом фокальных потерь ганглиозных клеток сетчатки (ГКС). Положительно коррелируют между собой уровень MMP-9 в сыворотке и объем фокальных потерь ГКС. Также выявлена отрицательная корреляция между ММП-7 и ТИМП-2 и положительная -между ММП-9 и ТИМП-2. Настоящее исследование показало, что у пациентов с СД 2-го типа и признаками нейродегенерации сетчатки имеется дисбаланс в системе матриксных металлопротеиназ и их ингибиторов. Ключевые слова: диабетическая ретинопатия, сахарный диабет, нейродегенерация, матриксные металлопротеиназы.

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-1, IL-17A, TNF, IFN, IL-10, TGF-1, TGF-2, TGF-3, 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-1 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-3 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.