Polymorphism of Transforming Growth Factor TGFB and Its Receptors TGFBRI, TGFBRII, TGFBRIIII Genes in Western Siberia Patients with Open-Angle Glaucoma.

Polymorphism of genes of transforming growth factor TGFB and its receptors (TGFBRI, TGFBRII, and TGFBRIIII) in patients with primary open-angle glaucoma was analyzed. The frequency of the TGFBRII CC genotype in patients is increased relative to the control group (OR=6.10, p=0.0028). Heterozygosity in this polymorphic position is reduced (OR=0.18, p=0.0052). As the effects of TGF-ß is mediated through its receptors, we analyzed complex of polymorphic variants of the studied loci in the genome of patients. Two protective complexes consisting only of receptor genes were identified: TGFBRI TT:TGFBRII CG (OR=0.10, p=0.02) and TGFBRII CG:TGFBRIII CG (OR=0.09, p=0.01). The study showed an association of TGFBRII polymorphism with primary open-angle glaucoma and the need to study functionally related genes in the development of the disease, which should contribute to its early diagnosis and prevention.

Studying the Proliferative Activity of Human Corneal Stromal Cell Populations.

The proliferative activity of populations of stromal cells (fibroblasts) obtained from human corneal lenticles under conditions of their differentiation into keratocytes was studied. It was shown that during differentiation, the number of dividing fibroblasts and the frequency of divisions, and motor activity of these cells (speed of movement along the cell trajectory and the length of the trajectory) sharply decreased. These findings indicate a decrease in the proliferative activity of fibroblasts under conditions of their differentiation and transformation into keratocytes. A period of 17 days is sufficient for differentiation of corneal fibroblasts into keratocytes.

Effect of Conditioned Media of Limbal Epithelial Cells and Corneal Stromal Cells on Functional Activity of Limb Mesenchymal Stem Cells.

We studied the effect of conditioned media from limbal epithelial stem cells, fibroblasts, and corneal keratocytes on the functional activity of human limbal mesenchymal stem cells. It was shown that the conditioned media from limbal epithelial stem cells reduced proliferative activity and inhibited migration of limbal mesenchymal stem cells. In the conditioned media of limbal epithelial stem cells, increased concentrations of VEGF and TNFα and reduced concentration of BDNF, vimentin, and fibronectin were found. The conditioned medium from corneal stromal cells did not affect functional activity of mesenchymal stem cells in the limbus. These data contribute to the understanding of the interaction of cells in the limbal niche and with corneal cells essential for the maintenance of the cellular homeostasis in the cornea.

Autophagy in Human Retinal Neurons in Glaucoma.

Immunohistochemical and ultrastructural analysis revealed signs of structural alterations in neurons and autophagy in all layers of the human retina at the end-stage glaucoma. The most pronounced destructive changes associated with swelling and destruction of mitochondria, endoplasmic reticulum, and Golgi apparatus, as well as structural signs of impaired synaptic activity and apoptosis were noted in ganglion, bipolar, and amacrine neurons. In the structure of photoreceptor cells, alone with destructive processes associated with structural alterations of rods and cones in the outer membrane discs, as well as swelling of organelles, we observed processes aimed at the maintenance of cell homeostasis. Structural signs of autophagy (mainly mitophagy) and changes of the ultrastructural organization in rod neurons were more pronounced than in cones.

Morphofunctional Properties of Corneal Stromal Cells.

Human corneal stromal cells were isolated by enzymatic digestion from a new source, lenticules obtained during laser vision correction by the ReLEx SMILe method. The resulting culture was mainly presented by fibroblast-like cells with a phenotype CD90-/CD73+/CD105+/keratocan-/lumican-/ALDH1A1+ that differentiate into keratocytes in a specialized medium. The concentration of fetal calf serum-derived growth factors affects the rate of proliferation, production of erythropoietin and brain neurotrophic factor by corneal fibroblasts, and to a lesser extent, their migration activity and production of extracellular matrix components. Thus, the high functional potential of fibroblast-like cells isolated from stromal lenticles can be used to develop cell technologies in ophthalmology.

Ultrastructural Organization of Uveal Melanoma Stromal Cells.

Typical blood capillaries and vessels in uveal melanoma were shown and different types of uveal melanoma stromal cells were determined by electron microscopy and immunohistochemical analysis. Macrophages, fibroblasts of varying degrees of differentiation and endothelial-like cells with numerous caveolae in the cytoplasm were found in the channels of the extracellular matrix surrounding accumulations of tumor cells. The presence local structures positively stained for markers of the blood and lymphatic vessels (CD31 and podoplanin) in channels of the extracellular matrix suggests that the described endothelial-like cells can be the structural basis for blood and lymphatic vessels of the tumor.

[Lymphatic system of the eye]. / Limfaticheskaia sistema glaza.

Existence of lymphatic outflow of intraocular fluid is still an open question. Identification of the lymphatic capillaries and vessels in various human organs in normal and pathological conditions became possible with discovery of endotheliocyte markers for lymphatic vessels. However, the available information on the presence of lymphatic structures in the human eye is inconsistent and uncertain. The data on lymphatic drainage of the eye is of interest, particularly because it may help understand glaucoma pathogenesis, mechanisms of development of eye inflammatory diseases, and develop pathogenetic therapies. The article reviews literature and presents the authors' own views on lymphatic drainage of the human eye.

[Cytokine gene polymorphisms in patients with age-related macular degeneration].

AIM: To establish possible association between age-related macular degeneration (AMD) and cytokine genotype polymorphisms; for that promoter regions of a number of cytokine genes were studied, namely, TNF-A863C, TNF-A308G, TNF-A238G, IL1ß-C-31T, IL4-C590T, IL6-C174G, and IL10A-1082G. MATERIAL AND METHODS: A total of 102 AMD and 100 non-AMD participants in the same age range were examined at the Novosibirsk branch of the Academician S.N. Fyodorov IRTC «Eye Microsurgery¼. In all cases restriction fragment length polymorphism analysis was performed. RESULTS: The frequency of TNF-308 GA and IL10-1082 GG genotypes was higher in AMD patients than in the controls, while the TNF-308 АA minor genotype has proved protective against the disease. Moreover, AMD has been found to be positively related to 48 genotypic combinations and negatively - to 32 (with specificity as high as 98-99%). The odds ratio was also higher in combination analysis as compared to monogenotypes. CONCLUSION: Complex genetic analysis of cytokines gives an idea of the balance of proinflammatory and anti-inflammatory cytokines in AMD and, therefore, plays an important role in studying the disease pathogenesis and exploring therapeutic options.

[THE STRUCTURE OF LYMPHATIC CAPILLARIES OF THE CILIARY BODY OF THE HUMAN EYE].

Using light microscopy, immunohistochemistry and electron microscopy, the structural organization of interstitial spaces and vessels of the ciliary body of the human eye (n = 5) were studied. The ciliary body was found to contain wide interstitial spaces--tissue clefts bound by collagen fibers and fibroblasts. Organ-specific lymphatic capillaries were also demonstrated in the ciliary body. According to the present findings and the lymphatic region concept, the first 2 elements of the lymphatic region of the eye were described: tissue clefts--prelymphatics and lymphatic capillaries of the ciliary body. The third element of the lymphatic region are the lymph nodes of the head and neck.

[Efficacy of azithromycin and its impact on cytokine system in urogenital infections].

Seventy five patients with urogenital chlamydial and mycoplasmic infections were enrolled in the trial. In the etiotropic therapy azithromycin was used in the standard dosage (1.0-1.5 g) depending on the infection. The treatment with azithromycin, in addition to the high eradication rates, was also evident of its effect on the cytokine levels in the patients, that was characteristic of a significant increase of the IFN-gamma level and a decrease of the IL-1beta and IL-6 levels in the blood.

[EFFECT OF THE POLYENZYME DRUG WOBENZYM ON THE ACTIVITY OF A DESTRUCTIVE INFLAMMATORY PROCESS IN THE COMPLEX THERAPY OF PULMONARY TUBERCULOSIS].

Ninety patients with new-onset pulmonary tuberculosis were examined prior to therapy The patients were randomized into 2 groups: 1) 20 patients receiving the standard antibiotic therapy regimen; 2) 70 patients taking the standard antibiotic therapy and the polyenzyme drug Wobenzym. The use of the latter in the complex therapy of patients with pulmonary tuberculosis was shown to cause an increase in the activity of the destructive inflammatory process and to regulate the function of the immune system as compared with those during the standard therapy.

Prooxidant-antioxidant factors in the blood of pregnant women with late gestosis of different severity.

Prooxidant-antioxidant factors were studied in the blood of pregnant women with gestosis of different severity. Comparative study showed that activation of peroxidation and decrease in the antioxidant potential depend on the severity of gestosis.

Content of proinflammatory cytokine in patients with clinical remission of chronic herpes infection during immunocorrection.

The concentrations of cytokines (interleukin-1beta, interleukin-6, and interferon-gamma) in blood plasma from patients with remission of chronic herpes infection were measured during immunocorrective therapy. Our results indicate that immunocorrection is pathogenetically substantiated and immunologically effective. It was manifested in reduction of inflammation and activation of antiviral protection.

[Study of the phases of development of humoral immune response]. / Izuchenie faz razvitiia gumoral'nogo immunnogo otveta.

In previously performed investigations to make clinical immunological diagnosis the principle of humoral immune response division into phases was put forward. The phases of humoral immune response were determined with lower content of immunoglobulins.