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Purpose: to study the structural organization of the vascular bed of human retina in the terminal stage of primary open-angle glaucoma (POAG).Material and methods. We performed a comparative immunohistochemical analysis of the content of vessels in the retina of 13 eyes of patients in the terminal stage of POAG, enucleated for medical reasons, and 17 eyes with uveal melanoma, using the markers of blood vessels endothelium CD34. The ultrastructural organization of the interstitium and endothelial cells of retinal microvessels was studied by electron microscopy and morphometry.Results. A significant increase in the volume density of the interstitium and a decrease in the volume density of CD34+-blood vessels in the retina of patients in the terminal stage of POAG, as compared with uveal melanoma, were revealed. An increased volume density of luminal and basal caveolae and the formation of transendothelial channels in the cytoplasm of endotheliocytes of retinal blood capillaries in the terminal stage of POAG were noted.Conclusion. In the terminal stage of POAG, the interstitial spaces of the retina are increased and the volume density of blood vessels is dropping. The increased volume density of luminal and basal caveolae and the formation of transendothelial channels in the cytoplasm of blood capillary endotheliocytes indicate the growth of transcytosis and the permeability of the blood-retinal barrier.

The endothelial NO synthase (eNOS) and vascular endothelial growth factor (VEGF) imbalance and the polymorphism of these genes may be the predisposition for diabetic retinopathy (DR) development and progression.The aim: to analyze VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes polymorphism and their combinations in patients with type 2 diabetes mellitus (DM2) with and without initial non-proliferative DR.Materials and methods. The study included 200 patients with type 2 diabetes (155 women and 45 men, age – 43–70 years): 111 people without and 89 people with DR. The polymorphism of the regulatory regions of VEGF (rs699947 and rs3025039) and eNOS (rs2070744) genes was studied using restriction fragment length polymorphism analysis and TaqMan Real-Time PCR by. Statistical processing was carried out using the software packages Statistica 10.0, SPSS Statistics 23 and the package of original programs for volumetric processing of bioinformation.Results. The VEGF-2578 heterozygosity and two complex genotypes – VEGF-2578CA:VEGF+936CC and NOS3-786CT:VEGF-2578CA:VEGF+936CC – signifi cantly decreased in patients with DR. The predisposition to early DR development to minor genotype of eNOS gene in the NOS3-786CC:VEGF+936CT complex and signifi cantly decreased the homozygous wild-type eNOS genotype in DM2 patients with ophthalmopathology were shown. NOS3-86TT:VEGF2578AA genotype signifi cantly decreased in group with retinopathy developing and the glycated hemoglobin high level.Conclusion. Along with the clinical risk factors for the development of DR in DM2, the genetic polymorphism of the regulatory regions of the genes analyzed by us has a signifi cant weight. When analyzing potential genetic markers, it is important to consider possible joint epistatic/hypostatic effects. The complex analysis of polymorphic gene can help early prognosis of the DR development.

The aim of this work was a comparative study of the ultrastructural organization of lymphatic structures in the choroid and conjunctiva of the human eye. Material and methods. Samples of the choroid and conjunctiva of the human eye, obtained perioperatively, were studied by immunohistochemical analysis using specific antibodies to endothelial cells markers of blood and lymphatic vessels, and electron microscopic studies, morphometric processing and statistical analysis of the results were performed. Results and discussion. Within simultaneous immunohistochemical staining of conjunctiva and choroid samples using antibodies to markers of lymphatic vessels (LYVE-1, Prox1, podoplanin) the positively stained typical lymphatic vessels have been revealed in the conjunctiva structure and positively stained channels with narrow elongated cells, fibroblasts and pigment cells in choriocapillar layer of the choroid and the transition zone between choroid and sclera. Electron microscopic study revealed that cells expressing lymphatic markers and forming lymphatic channels in the choroid have an ultrastructural organization that is differ from typical lymphatic vascular endothelial cells: they do not have stropic filaments, contain a greater volume density of the granular endoplasmic reticulum membranes, and a lower volume density of mitochondria and micropinocytotic vesicles. The data obtained indicate that the lymphatic pathways of the intraocular fluid outflow in the human eye choroid have organ-specific structural features.

Purpose. To study the content of cytokines and growth factors in the intraocular fluid of patients with developed stage of primary open-angle glaucoma (POAG).Materials and methods. 56 patients with a verified diagnosis developed stage of primary open-angle glaucomawere examined. The control group consisted of 30 patients with a diagnosis of uncomplicated cataract. A concentration of 17 cytokinesand 3 isoforms of the transforming growth factor (TGF) β was determined using a Bio-Plex Pro™ Human Cytokine 17-plex Assay and Bio-Plex Pro™ and TGFβ 3-plex Assay kit by flow-through fluorometry on a Bio-Plex 200, Bio-Rad double beam laser analyzer, USA.Results. Astatistically significant increase was shown in the concentrations of cytokines and growth factors (interleukins (IL) 4, 6, 7, 8, 12, 17, TGFβ 1, 2, 3, macrophage inflammatory protein 1 β) in the intraocular fluid of patients with developed stage of the primary open-angle glaucoma in respect to data obtained from the study of the intraocular fluid of the persons with uncomplicated cataract, as well as a statistically significant decrease in the concentrations IL-2, IL-10, granulocyte-macrophage colony-stimulating factor.Conclusion. In the pathogenesis of primary open-angle glaucoma, the activity of the local chronic inflammatory process is determined. This is confirmed by statistically significant changes in the studied cytokines and growth factors. Increase in the concentrations of the studied representatives of the superfamily of transforming growth factors-beta, which have anti-inflammatory activity, the ability to stimulate proliferation, cell growth, synthesis of extracellular matrix proteins, etc., attests to their importance in the mechanisms of primary open-angle glaucoma development. Increase concentrations of IL-7 in the intraocular fluid of patients with primary open-angle glaucoma allows us to assume participation in the pathogenesis of the primary open-angle glaucoma of this autocrine mediator of activation of the growth of lymphatic structures.

Purpose: to study the content of proinflammatory cytokines IL-6, IL-8 and IL-17 in lacrimal and intraocular fluid in patients with advanced stage of primary open-angle glaucoma. Material and methods. The study included 56 patients with advanced stage diagnosis of primary open-angle glaucoma (POAG). The diagnosis was determined by ophthalmological examination, including visual acuity, binocular ophthalmoscopy, spheroperimetry, echoophthalmography, optical coherence tomography, intraocular pressure measurement. The number of men was 21 (37.5 %), women - 35 (62.5 %), the average age of patients was 62.8 ± 4.3 years. Exclusion criteria were acute and exacerbation of chronic inflammatory diseases of the organ of vision, diabetic retinopathy, neovascular glaucoma, uveitis, hemophthalmia, autoimmune and tumor processes of any localization, as well as acute and exacerbations of chronic inflammatory diseases of any organs and systems. Patients who took drugs containing prostaglandins analogues for intraocular pressure normalization, that could activate the inflammatory process, were excluded from the study. A comparison group was composed of 30 patients with the uncomplicated cataract diagnosis. All patients underwent the determination of IL-6, IL-8, IL-17 in the lacrimal and intraocular fluid. Results. It has been established that the significant increase in the concentrations of IL-6, IL-8 and IL-17A in the lacrimal and intraocular fluid was revealed in patients with advanced stage of POAG in comparison with those obtained in patients with uncomplicated cataracts. The obtained data testify to the presence of local destructive-inflammatory process in the mechanisms of the development of primary open-angle glaucoma. The revealed unidirectional change in the concentrations of IL-6 (2.8 times the lacrimal fluid and 5.2 times in the intraocular fluid), IL-8 (1.5 times in the lacrimal fluid and 4 times in the aqueous humor), IL-17 (1.75 times in lacrimal fluid and 1.95 times in the intraocular fluid) allows us to conclude that lacrimal fluid can be used to assess changes in cytokine content in the pathogenesis of ophthalmic diseases.

Purpose. To conduct a comparative study of cellular and subcellular components of tear fluid of healthy persons (HP), those suffering from primary open-angle glaucoma (POAG), and patients with diabetic retinopathy (DR). Material and methods. Electron microscopy of ultrathin sections was used to test tear samples of 16 patients with initial POAG, 9 patients with developed POAG, and 6 with an advanced stage of POAG. Besides, 12 patients with proliferative DR (PD) and 6 patients with nonproliferative DR (NPD) were tested. Tear samples of 29 subjects with no ophthalmic pathology served as control. Results. All the examined samples contained cells, cellular fragments and debris, mucous granules and lipid structures. The occurrence of all these structures was found to be different in the tears of diabetic and glaucomatous patients as compared to that of HP. The share of epithelial cells in the tear of patients with the initial stage of POAG was twice as high as in the control group; then it drops gradually so that in the advanced stage, epithelial cells are not detected. The tear of NPD patients shows an increase of the content of mucin and lipids against the control, while in PD it is lower than in HP. Leukocytes were observed in the tear of a quarter of HP, while in diabetic patients leukocytes show a significant increase, which reflect a higher permeability of blood vessels as the disease develops. There were no leukocytes in tear samples of all patients with POAG, which may be associated with damaged functions of the blood vessel wall. We found “hairy” vesicles in the tear which had not been noted previously; the amount of these vesicles was growing at early stages of POAG and DR. Conclusion. Electron microscopy of tear deposits evaluates the state of the cornea and the conjunctiva, as well as goblet cells and the meibomian glands. It reveals signs of permeability change in tissue vessels adjacent to the anterior area of the eye. For the first timechanges in tear components in glaucomatous and diabetic patients, were found: theses changes may in future be used to achieve early diagnosis of these diseases // Russian Ophthalmological Journal, 2017; 1: 56-62. doi: 10.21516/2072-0076-2017-10-1-56-62.

Diabetic retinopathy (DR) is one of the leading causes of avoidable blindness worldwide. Chronic low-grade inflammation and abnormal angiogenesis, which is considered to be principal components of DR pathogenesis, is accompanied by imbalance in cytokine production. It was shown that single-nucleotide polymorphisms (SNPs) in the promoters of cytokine genes affect the cytokine production in normal and pathological conditions. Accordingly, we aimed to assess the frequencies of combinations of SNPs from promoters of cytokine genes in type 2 diabetic subjects with and without DR.Materials and methods: We enrolled 201 caucasian subjects with type 2 diabetes, including 90 ones with non-proliferative or preproliferative retinopathy and 111 subjects without DR. Eight SNPs, located in the gene promoters of TNFA (rs1800630, rs1800629, rs361525), IL1B (rs1143627), IL4 (rs2243250), IL6 (rs1800795) and IL10 (r1800896, rs1800872), were investigated. In groups of patients with and without DR, the frequencies of alleles, genotypes and their combinations, odds ratios and specificity were calculated. The networks between genes and quartiles of glycated hemoglobin A1c (HbA1c) were visualized with Cytoscape.Results. We revealed 36 combinations of SNPs with different frequencies in the groups of patients with and without DR. In the combinations associated with DR with a specificity >99% homozygous GG genotype in position -174 of IL6 (rs1800795), CT genotype in position -31 of IL1B (rs1143627), СС genotype in position -592 of IL10 (rs1800872), CT genotype in position -590 of IL4 (rs2243250) were the most frequently detected variants. High levels of HbA1c (>9.8%) were associated with combinations of CA genotype in position -863 TNFA (rs1800630) with homozygous variants GG in positions -238 and -308 TNFA (rs1800629, rs361525).Conclusion. Genetic combinations, associated with DR in type 2 diabetic subjects, include homozygous variants in polymorphic positions of the gene promoters of IL6 (rs1800795), IL1B (rs1143627) and TNFA (rs1800630, rs1800629, rs361525). The combinations of the variants of cytokine genes with a high level of HbA1c can be an important mechanism for realizing of individual genetic predisposition to the development of DR.

Age-related macular degeneration is one of the most widespread multifactorial eye diseases. Polymorphic functional alleles of vascular endothelial growth factor (VEGF) combined with matrix metalloproteinase (MMP) gene and tumor necrosis factor (TNF) gene variants may influence the development of disease. We have performed frequency analysis of their polymorphisms in regulatory regions of VEGF (rs 699947, rs 3025039), ММР2 (rs 2438650), ММР3 (rs 3025058), ММР9 (rs 3918242), TNFα (rs1800630, rs1800629, rs 361525) genes, and their combinations in a group of patients with age-related macular degeneration (MD). Frequencies of TNFα (rs1800629) genotypes significantly differed for the MD patients and control group. Upon the combined genotype analysis, we have revealed six constellations of VEGF-ММР genes that were positively associated with the disease development. Five of them included minor homozygous genotype VEGF-2578АА. A combined analysis of VEGF – TNFα genes polymorphisms has shown presence of both positive and negative complex genotypes. The most significant differences have been detected by comparative analysis of the complex genotypes frequencies which included 8 polymorphic regulatory gene regions of all genes studied. In most genetic complexes associated with the disease development, homozygous TNFα-863СС, homozygous MMP2-1306 ТТ, and MMP9-1562СС genotypes have been detected, together with the combination of homozygous VEGFA+936СС genotype in the same patients. We can assume that harboring allelic variants, which may contribute to angiogenesis prorcesses is typical for the genome of patients with macular degeneration, along with low-level production of pro-inflammatory regulatory factors and enzymes participating in degradation of extracellular matrix. Analysis of complex genetic factors, procing some factors taking part at the pathological process being the regulators of production for each other, is more informative when detecting protective and resistant markers of the disease development rather than single genetic markers, thus being useful for genomic screening.

The review presents information of contemporary scientific literature regarding the role of the various classes of cytokines and growth factors in the pathogenesis of proliferative diabetic retinopathy (PDR). Information of the role in the PDR pathogenesis of biologically active molecules, involved in the inflammatory and angio-proliferative processes, is a basis for the selection of potential molecular targets for the development of new bio-engineering drugs.

Purpose. To detect and study the structure of aqueous humor lymphatic outflow pathways in choroid in normotensive patients and patients with primary open-angle glaucoma (POAG).Material and methods. Choroid fragments of seven human eyes (including two eyes with terminal glaucoma) enucleated on medical indications were studied. The structure of the choroid was investigated using immunohistochemistry and electron microscopy.Results. Lymphatic channels and lymphatic lacunae were revealed in the choroid structure. Lymphatic channels were detected in choriocapillar and vascular layers and were limited by Podoplanin+, Prox-1+, LYVE-1+ endothelium-like cells, fibroblasts and pigment cells. Lymphatic lacunae were located in suprachoroid layer and covered with endothelium-like cells and fibroblasts. Morphometric study showed an increase of the volume density of epithelium, interstitial spaces and choroid vessels related to edema and swelling of the choroidal stroma in the terminal stage of glaucoma.Conclusions. Human choroid contains lymphatic structures that are probably a part of the ocular lymphatic drainage system and participate in the aqueous humor outflow. Choroidal edema and swelling, the increase of the volume density of epithelium, interstitial spaces and choroid vessels in the terminal POAG stage indicate the lymphatic drainage dysfunction beginning from initial stages of glaucoma and lead to an aqueous humor outflow alteration through the protective lymphatic system.

Purpose. To evaluate the possibility of application of electron microscopic analysis of human lacrimal fluid (LF) in the development of methods for early diagnosis and prognosis of ophthalmic diseases.Material and methods. Specimens of the reflex LF were collected from the lower conjunctival arch of eyes in 20 patients with a diagnosis of diabetic retinopathy, hyperopia, glaucoma, cataract and macular degeneration, and pelleted by centrifugation. The liquid portion of LF was examined by the negative staining method, and the pellets were processed by the ultrathin sectioning method, and the sections were studied in the electron microscope JEM-1400 (JEOL, Japan).Results. The liquid portion of LF contained macromolecular aggregates, microparticles and exosomes, the number and morphology of which varied depending on the eye disease. Ultrathin sections of the LF pellets showed fibrous matrix, epithelial cells, lymphocytes and polymorphonuclear leukocytes, cell debris, and small roundish vesicles (150- 300 nm) on the surface bearing the protein «filaments» penetrating inside. The cellular composition of LF pellets varied depending on the disease of eye.Conclusions. Identification of the obvious differences in the content and morphology of the structural components of the LF indicates a high diagnostic potential of the LF. Electron microscopy of LF looks promising for a search of ultrastructural diagnostic and prognostic markers of ophthalmic diseases.

Purpose. To identify and study an organization of structures providing the lymphatic drainage of aqueous humor in the anterior chamber of the human eye.Material and methods. The eye fragments enucleated for medical reasons (n=5) were used as research objects. Electron microscopic and immunohistochemical study of eye tissues was carried out.Results. The organ-specific lymphatic capillaries in the ciliary body and structured interstitial spaces – tissue gaps bounded by collagen fibers and fibroblasts in the anterior segment of the human eye were revealed by using immunohistochemical and electron microscopy studies.Conclusions. It is proposed to consider the lymphatic region of the eye where on the basis of the obtained data the first 2 links were allocated - tissue gaps – prelymphatics and lymphatic capillaries of the ciliary body. Structured pathways of aqueous humor outflow can determine the eye trophic and drainage status, intraocular pressure and the function of the ocular organ.

Introduction. An urgent interdisciplinary problem is the identification of factors that determine the processes of constructing social identity, which is the socio-cultural foundation of the existence of any community. The aim of the work is to identify the actual role and potential of artistic and aesthetic components of social space in the process of forming the regional identity of the youth. Materials and Methods. The empirical basis of the study was the data of a questionnaire survey of the youth of Moscow and the Moscow region, Penza and Saratov regions (n = 1000) and interviews with representatives of the student youth of Saratov and Penza (n = 30), devoted to the analysis of the identification hierarchy of the youth and the influence of aesthetic components of the social space of the region on the formation of its regional identity. These methods revealed the important role of artistic and aesthetic components of the regional social space in the construction of regional identity and regional patriotism of the youth of the region. Results. Based on the results of the research, a conclusion has been made about the connection between “local” patriotism and specific social attitudes focused on the development of the territorial community and the improvement of its image, as well as about the partial determinism of the regional components of the respondents’ social identity by figurative and aesthetic factors. It is shown that at the theoretical level, taking into account the aesthetic factors of the construction of social identity implies a transition from deterministic models of interaction in the system “social environment – emerging personality” to stochastic ones. Discussion and Conclusion. The authors point out when modeling the process of forming the social identity of young people, theoretical models based on the concepts of social constructivism should take into account the unique, intimate-personal interactions of a particular individual with separate socio-cultural phenomena symbolizing collective identity. The results of the study can be used by all agents of socialization in the practice of applying aesthetic components of regional social space in the process of forming regional patriotism.

Ethno-regional parties play a vital role in the conflict between the center and the ethnic regions, which is relevant for all modern multiethnic EU states. The European integration allows these parties to participate in the regional policy of the EU (contributing to the decentralizing reforms in the member states), as well as to interact within Euroregions and on communitarian platforms, such as the European Parliament. This article aims to clarify if this ethno-regionalist faction is able to influence the integration processes in Europe, and to what extent. To achieve this goal, we need to answer the following questions: how can the ethno-regionalists be described from a theoretical point of view? What is the dynamic of their development within the European Parliament, considering the historical retrospective? What are their current ideological attitudes that allow them to maintain unity and achieve success? The article is based on the author’s concept of cultural-territorial differentiations, which points the correlation between the political ethno-regional movement and the existing ethnocultural features and historical territory. The author concludes that it was Europeanization that led to the strengthening of the ethno-regional movement in Europe as it made the question of the ethno-regional collective response relevant. Therefore, ethno-regionalists are an essential element of every political system at the national and supranational levels. At the same time, the historical evolution and experience of European regionalists prove that they cannot constitute an independent and autonomous political force at the supranational level as their cooperation depends on various legal and political circumstances occurring on the state level.

Aim. To reveal cognitive deficit after coronary artery bypass, the influence of citicoline, piribedil on the state of higher cerebral functions in the early and late periods after surgery.Material and methods. The study included 94 patients with ischemic heart disease. All patients were divided into 3 groups. Patients of the first group (n=30) were prescribed citicoline as a cerebral neuroprotective drug. Patients of the second group (n=32) had piribedil in addition to standard therapy. Patients of the control group (n=32) had only a standard treatment without any neuroprotective drugs. All patients underwent coronary artery bypass surgery. The cognitive function was assessed before, 10 days after and six months after coronary artery bypass.Results. Patients of group 1 and 2 had achieved pre-surgical levels of cognitive tests results 6 months after coronary artery bypass. The control group had achieved initial levels only in three tests: visual memory (immediate simulation; p=0.008), categorical association (p=0.002), clock drawing test (Wilcoxon test; p=0,005), while other indices were reduced in comparison with the initial ones.Conclusion. The obtained results allow considering the studied drugs as a protectors of cognitive function after surgery. Randomized controlled double-blind studies on large samples are needed to confirm these results.

AIM. To evaluate the efficacy of the combined drug furamag (furasidine potassium and magnesium hydroxycarbonate) in combination with the third-generation cephalosporin cefotaxime versus cephalosporin monotherapy for nosocomial urinary tract infections (NUTI). MATERIALS AND METHODS. The randomized open-label comparative parallel group clinical trial enrolled 52 male and female patients aged over 18 years with a documented diagnosis of NUTI. Group 1 (a study group) took oral furamag 300 mg/day in combination with intravenous cefotaxime 6 g/day; Group 2 (a control group) received cefotaxime monotherapy. The duration of therapy in both groups was 7 to 10 days until the efficiency levels were achieved. RESULTS. A final efficiency analysis was made in 24 and 25 patients from Groups 1 and 2 who had different forms of NUTI (catheter-associated NUTI, cystitis, pyelonephritis). On day 3 of treatment, most patients were noted to have a decreased systemic inflammatory response; lower C-reactive protein and procalcitonin levels being in the study group patients. The clinical efficiency of antibacterial therapy, which had been evaluated both immediately after treatment termination and during further control, did not substantially differ in the furamag/cefotaxime combination and control groups although there was an obvious tendency towards the more marked effect of combined therapy 7-14 days after treatment (11.8% efficiency differences; p>0.05). Analysis of bacteriological efficacy revealed its most pronounced and clinically significant differences between the groups: the cefotaxime/furamag combination led to higher pathogen eradication in all follow-up periods: after 3 days of treatment (82.6%) and following a complete therapy cycle (95.8%) versus the cefotaxime monotherapy group (43.5 and 70.8%, respectively; p