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The article presents a literature review of the modern concept of anatomical and physiological structure and functioning of the cornea. The strict morphological structure and corneal tissue homeostasis ensure its transparency. Studying the mechanisms that regulate the constancy of the corneal tissue internal environment allows us to get closer to understanding the prospects forregenerative therapy for the corneal stroma pathology. The article discusses in detail the role and functional potential of corneal stromal cells, which are capable of reverse cytologic differentiation, which primarily ensures the maintenance of tissue homeostasis and corneal transparency. The functional activity of corneal cells can change for a number of reasons, which may be exogenous, iatrogenic (trauma, infection, etc.) or endogenous. Endogenous causes include: cell autoregulation pathologies (for example, enzyme defects); defects in transport systems leading to tissue hypoxia; disorders of the neuro-humoral regulation of trophism. The physical reason forthe violation of the corneal transparency is an increase in the light scattering. The article presents five main causes of increased light scattering in the opaque cornea, and also provides an overview of the main substances – components and products of cellular synthesis of corneal stromal cells: cytokines and growth factors (complex of the signal molecule and the SDF1/CXCR4 receptor, insulin-like growth factor 1, tumor necrosis factor alpha, intercellular adhesion molecule 1, erythropoietin, neurotrophic factors, etc.). Thus, corneal opacity can be caused by a single pathogenic mechanism or be the result of a complex effect of several factors. The main processes of tissue homeostasis regulation are aimed at maintaining the unique morphological structure of the cornea.

Abnormal expression of matrix metalloproteinases (MMP) in watery moisture in patients with glaucoma may affect regulation of intraocular pressure (IOP). MMP activity is regulated by tissue metalloproteinase inhibitors (TIMP). The imbalance between tissue metalloproteinase inhibitors and matrix metalloproteinases may contribute to the development of glaucoma. Genetic factors, including polymorphism of matrix metalloproteinase genes and their inhibitors genes, can regulate the level of their expression, thereby affecting susceptibility to disease. Our aim was to perform comprehensive analysis of the MMP2 (rs243865), MMP3 (rs3025058), MMP9 (rs3918242) polymorphisms, and TIMP1 (rs4898), TIMP2 (rs8179090) tissue inhibitor genes polymorphisms in the patients with stage II (advanced) primary open-angle glaucoma.99 patients (52 men and 47 women) with a verified diagnosis of stage II primary open-angle glaucoma were examined. The comparison group consisted of 100 age-matched persons (81 women and 19 men) without ophthalmic disorders. The single-nucleotide polymorphisms in promoter regions of MMP2, TIMP1, TIMP2 genes were analyzed by the TaqMan method, the MMP3 and MMP9 genes, by means of restriction fragment length polymorphism technique. Statistical evaluation was carried out using the specialized package of IBM SPSS Statistics 23 programs. The critical level of significance was assumed to be 0.05.The differences in the distribution of MMP2 rs243865 allelotypes with decreased frequency of TT genotype were found in the patient group and, vice versa, increased heterozygosity rates were revealed among them. In addition, the frequency of TIMP1 rs4898 heterozygous genotype was decreased in this group as compared to control sample. Four MMP/TIMP complex genotypes are positively associated with the development of pathology. Two of them were of bilocus type, i.e., MMP2-1306TC:TIMP2-418GG, and MMP3-11715A6A:TIMP1 372CC whereas two three-locus constellations were revealed, i.e., MMP2-1306TC:MMP9-1562CC:TIMP2- 418GG, and MMP3-11715A6A:MMP9-1562CC:TIMP1 372CC. There are nine MMP/TIMP complexes, the frequency of which in patients with glaucoma was significantly reduced when compared with control group.Polymorphism of regulatory regions of MMP2, MMP3, MMP9 genes and distinct gene variants of their inhibitors (TIMP1, TIMP2 genes) can be considered potential markers of the POAG development associated with an imbalance of MMP/TIMP activities.

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 aim: to conduct a clinical and diagnostic evaluation of the effectiveness of the administration of a complex of drugs in the region of hemolymphocirculation in optical neuropathy in patients with edematous form of endocrine ophthalmopathy.Materials and methods. The results of diagnosis and treatment of 31 patients (61 eyes) with optical neuropathy on the background of edematous exophthalmos in endocrine ophthalmopathy were analyzed. To identify hidden forms of optical neuropathy, such studies were prescribed as computer microperimetry on a confocal infrared ophthalmoscope, a complex of electroretinographic studies: registration of maximum ERG, oscillatory potentials. Latent forms of optical neuropathy were detected in 22 cases. In 9 cases, there were obvious forms of optical neuropathy. All patients underwent a 10-day course of intensive complex treatment, consisting of injections into the region of hemolymphocirculation (projection of the pterygoid fossa) No. 6–8 (No. 3–4 on each side) with an interval of 24 hours of a drug mixture, the formulation of which included Lidocaine 20 mg, Dexazone 4 mg, Hemase 3000 UNITS, Dalargin 1 mg.Results. In all patients, there was a pronounced positive dynamics in the form of a significant (from 0.6 to 1.0) increase in visual acuity, a decrease in exophthalmos from (2.0 to 3.0 mm), an increase in color and contrast sensitivity.Conclusions. Due to the violation of venous and lymphatic outflow due to thickening of extraocular muscles and retrobulbar fiber, injections into the hemolymphocirculation region (projection of the pterygoid fossa) of drugs with a wide range of decongestant and metabolic effects are justified, effective and safe.

Aim. To study the content of matrix metalloproteinase (MMP)-2, -3, -9 and tissue inhibitors of metalloproteinases (TIMPs) -1, -2, -3, -4 in the aqueous humor of patients with moderate primary open-angle glaucoma (POAG).Materials and methods. The experimental group included 47 patients with verified moderate primary open-angle glaucoma. The control group consisted of 26 patients with uncomplicated cataract. The levels of MMP-2, -3, -9 were determined with Luminex Performance Human MMP Magnetic Panel 3-plex kit (R&D Systems, USA), the concentration of TIMPs-1, -2, -3, - 4 was determined with the Human TIMP Magnetic Luminex Performance Assay 4-plex kit (R&D Systems, USA). The study was carried out using flow-through field fluorometry on a Bio-Plex 200 double-beam laser analyzer (Bio-Rad, USA).Results. The study showed a statistically significant increase in the levels of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinases-1, -2, -3, -4 in the aqueous humor of patients with moderate POAG compared with patients with uncomplicated cataract.Conclusion. The obtained data on high concentrations and imbalance in the levels of matrix metalloproteinases and their tissue inhibitors in the aqueous humor of patients with moderate POAG confirm the role of local inflammation, as well as impairments in the structure of the extracellular matrix and its remodeling in the mechanisms of development of this pathology.

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.

Aim. To determine the presence or absence of specific IgG antibodies against SARS-CoV-2 antigens in outpatient clinic staff and to compare clinical and immunological features from April to August 2020.Materials and Methods. The control group comprised 386 employees of the Novosibirsk City Clinical Polyclinic №13.The determination of IgG antibodies against SARS-CoV-2 antigens in blood serum was performed by using the ELISA method. A real time method of reverse transcription and polymerase chain reaction was used to extract RNA SARS-CoV-2 from nasopharyngeal and oropharyngeal swabs.Results. Specific IgG antibodies against SARS-CoV-2 antigens were detected in 32 (8.42%) employees of the polyclinic. Antibodies were not detected in 91.58% of employees. 9 members (28.12%) had clinical symptoms of varying degrees of disease severity in the group of employees with the presence of antibodies, 4 members of this group (12,51%) had bilateral community-acquired pneumonia with signs of COVID infection, another 5 members (15.61%) with antibodies had signs of ARVI of mild and moderate severity. RNA SARS-CoV-2 in the group of employees with the presence of antibodies and clinical implications was not detected in any case; 23 (71.88%) members with the presence of IgG-antibodies did not have clinical implications of the disease.Conclusion. The presence of specific antibodies against SARS-CoV-2 in employees with clinical implications of COVID-19 without detection of the RNA virus in the biological material is a retrospective confirmation of the etiology of the transferred infection. The detection of specific antibodies in persons who did not have clinical implications can serve as confirmation of the asymptomatic course of the transferred coronavirus infection.

The review presents data from contemporary scientific literature regarding the role of the various classes of cytokines and growth factors in the pathogenesis of in the pathogenesis of primary openangle glaucoma. Information of the role in the mechanisms of glaucoma development of biologically active molecules, involved in the inflammatory and proliferative processes, is a basis for studying the pathogenesis of the pathological process and creating new approaches to treatment. glaucoma; inflammation; cytokines; growth factors

Background. In recent years, the studies concerning the role of melatonin and cytokines in the development of various pathological processes have been conducted in various fields of medicine, including ophthalmology.Purpose. To study the effect of melatonin-containing therapy on the concentration of pro-inflammatory cytokines, melatonin in the lacrimal fluid and melatonin in the blood serum in patients with non-exudative AMD in the course of surgery for uncomplicated senile cataract. Material and methods. During the study, 2 groups have been formed: group 1 (main group) – 40 patients who took the drug «Melaxen» (3 mg at night) for 3 months before the surgery; group 2 (control group) – 40 patients who did not take melatonin before the surgery. Laboratory studies of blood samples and tear fluid for the hormone melatonin and cytokines (IL-1β and IL-8) were carried out using enzyme-linked immunosorbent assay.Results. When taking exogenous melatonin in patients of the main group, the concentration of melatonin in blood serum and lacrimal fluid was significantly higher during the entire observation period, compared with the control group patients. Also, melatonin-containing therapy contributed to a decrease in the concentration of pro-inflammatory IL-8 and IL-1β cytokines. A correlation analysis of the level of cytokines and the content of melatonin in lacrimal fluid of the examined groups patients revealed a significantly higher feedback before surgery and significantly weaker and direct after the surgery.Conclusion. An increase in the concentration of melatonin in the lacrimal fluid after surgery for senile cataract in both groups indicates a possible increase in its production in response to surgical treatment and is aimed at reducing the activity of the local inflammatory process. The obtained results allow us to conclude that melatonin has an antiinflammatory effect.

Purpose. To evaluate the clinical-ophthalmic effectiveness of using of autologous platelet-rich plasma as part of a comprehensive treatment regimen for uveitis associated with systemic diseases and accompanied by macular edema.Material and methods. The study included 120 people (176 eyes) from 18 to 50 years old with uveitis associated with systemic diseases, accompanied by macular edema: 46 men, 74 women. Patients were divided into 2 groups: the main group consisted of patients receiving antiinflammatory treatment and autologous platelet-rich plasma application; control group consisted of patients receiving anti-inflammatory treatment. All patients underwent a comprehensive ophthalmological examination.Results. It was found that autologous platelet-rich plasma application during anti-inflammatory treatment for patients with uveitis associated with systemic diseases and accompanied by macular edema improves best-corrected visual acuity, statistically significant decrease in retinal thickness in fovea and increase in retinal photosensitivity relative to the data obtained in the control group.Conclusion. The use of autologous platelet-rich plasma in combination with anti-inflammatory treatment decreases incidence of relapse of uveitis associated with systemic diseases, contributes to reducing macular edema and improving functional performance.

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-γ level and a decrease of the IL-β and IL-6 levels in the blood.

The purpose of the study was to examine the characteristics of the content of cytokines in the peritoneal fluid in women of reproductive age with infertility against the background of chronic inflammatory diseases of the pelvic organs in the stage of clinical remission.Material and methods. A study was conducted of 50 patients aged 23-36 years with a verified diagnosis of infertility of tubal peritoneal genesis against a background of chronic inflammatory diseases of the reproductive sphere in the stage of clinical remission. As a control group, 15 practically healthy women aged 25-37 years were examined. Concentration of cytokines TNF-a, IL-4, IL-6, IL-10, IFN-y, MCP-1 in the peritoneal fluid was measured by enzyme-linked immunosorbent assay.Results and discussion. In the main group of patients with tubal-peritoneal infertility, the activity of local inflammatory reactions is tested in the period of clinical remission of a chronic inflammatory process. This is confirmed by a significantly higher level of TNF-a, IL-4, IL-6, IFN-y, MCP-1 in the peritoneal fluid compared to the control group. The studied biologically active substances play a significant role in the development of the immune response, as well as fibroplastic processes. The results can be regarded as the latent development of the immune response in reactions to constant antigenic stimulation from the focus of chronic inflammation, which is a significant factor in the development of adhesions in the formation of infertility, and requires the inclusion of immunotropic therapy methods in treatment.

Purpose. To study the concentration of cytokines and growth factors in the aqueous humor of patients with congenital aniridia.Patients and methods. The study comprised 10 patients (10 eyes) with congenital aniridia and 10 patients (10 eyes) with agerelated cataract. Aqueous humor was collected at the beginning of routine cataract surgery before the primary incision was created. A concentration of 27 cytokines and the transforming growth factor-β2 (TGF- β2) was determined using a Bio-Plex Pro™ Human Cytokine 27-plex Assay and Bio-Plex Pro™ and TGFβ 3-plex Assay kit by flow-through fluorometry on a Bio-Rad MAGPIX (Luminex Corp. Austin). Intergroup comparisons were conducted using the Mann-Whitney U test. Results. A comparative analysis showed a statistically significant increase in the concentration of IL-7 (p = 0.004), IL-15 (p = 0.008) and a decrease in the content of IL-9 (p = 0.008), IL-10 (p = 0.034) and GM-CSF (p = 0.045) in patients with congenital aniridia compared with the age-related cataract group. Inflammatory mediators (IL-1β, IL-6, IL-8, IL-12, IL-17A, MCP-1) and vascular endothelial growth factor (VEGF) in the aniridia group did not statistically differ from the comparison group.Conclusion. Statistically significant difference was detected in IL-7, IL-9, IL-10, IL-15, GM-CSF concentrations in the aqueous humor in patients with congenital aniridia when comparing to non aniridic patients with age-related cataract. The other cytokines with proinflammatory, angiogenic and profibrotic properties did not significantly differ from the comparison group.

Purpose: to study the clinical and laboratory efficacy of the platelet autoplasma use in the complex treatment of endogenous uveitis associated with systemic diseases accompanied by macular edema. Material and methods. The study included 46 people (72 eyes) with endogenous uveitis and macular edema. The diagnosis was made on the basis of the ophthalmological examination, including visometry, tonometry, biomicroscopy, ophthalmoscopy, perimetry, B-scan, optical coherence tomography of the macular zone, photoregistration of the anterior, posterior segment of the eye. The examination was carried out on the 1st and 10th day of treatment. The main group consisted of 22 people (36 eyes) who underwent anti-inflammatory therapy and the introduction of platelet plasma in the region of the pterygopalatine fossa. The control group consisted of 24 people (36 eyes) receiving only anti-inflammatory therapy (diprospan 0.5 paraequatorially №1, dexazone 4 mg intravenously №5, intravenous lasix 2.0 ml №5, electrophoresis with prednisolone № 7). All patients underwent the definition of IL-4, IL-6, IL-8, IL-17 in tear fluid before the study and on the 10th day. Results. The significant increase in the concentrations of pro-inflammatory cytokines (IL-17A and IL-8) and IL-4 and IL-6 involved in the development of autoimmune response and chronic inflammation was found in the patients with endogenous uveitis and macular edema. The use in the treatment of endogenous uveitis with macular edema of platelet autoplasma leads to more pronounced improvement of clinico-ophthalmological parameters (improvement in visual acuity, retinal photosensitivity, and retinal thickness reduction) relating to the comparison group. A decrease in the activity of the inflammatory process was noted in the main group after treatment, which is manifested by a significant decrease in the concentrations of IL-17A, IL-8, IL-4, IL-6, relating to the data obtained in the comparison group. The proposed scheme of complex treatment allows reducing the frequency of relapses of the pathological process.

Background. A common cause of visual impairment in patients with non-infectious uveitis is macular edema, developing in 38–84 % of cases. Plasma enriched with platelets is widely used in various branches of medicine, the effectiveness of its use in the treatment of non-infectious uveitis, accompanied by macular edema, has not been sufficiently investigated. Aim: To evaluate the effectiveness of autologous platelet-rich plasma in the complex treatment of non-infectious uveitis accompanied by macular edema.Material and methods. The study was conducted on the basis of the academician S.N. Fyodorov Eye Microsurgery Federal State Institution in the period from 2016 to 2018, which included 123 people (176 eyes) from 18 to 50 years with non-infectious uveitis, accompanied by macular edema: 46 men, 77 women. Patients were divided into 2 groups. The main group consisted of patients receiving autologous platelet-rich plasma and anti-inflammatory treatment; the comparison group consisted of patients receiving anti-inflammatory treatment. The results of visual acuity, intraocular pressure, biomicroophthalmoscopy, optical coherence tomography of the macular zone, microperimetry, ultrasound examination on the side of the affected eye were evaluated. Statistical processing of the data was carried out in the program Statistica 10.Results. Maintenance of autologous platelet-rich plasma contributes to a statistically significant improvement in visual acuity on the 10th day of treatment by 64.2 %, a decrease in the thickness of the retina in fovea by 36.3 % and an increase in retinal photosensitivity by 34.6 % compared to the group of patients receiving only anti-inflammatory treatment. Conclusions. The use of autologous platelet-rich plasma in the complex treatment of non-infectious uveitis allows to accelerate the natural mechanisms of tissue regeneration, contributing to the reduction of macular edema, and improve visual performance.

Purpose. To study transforming growth factors – beta 1,2,3 (TGF-β1, TGF-β2, TGF-β3) in intraocular aqueous humor (AH) of patients with the advanced stage of primary open angle glaucoma (POAG).Material and methods. The study included an examination of 56 patients with advanced stage of POAG which comprised the main group. The diagnosis of POAG was confirmed based on ophthalmological examination. The control group consisted of 30 patients with uncomplicated cataract. TGF-β isoforms concentrations were detected by flow fluorimetry using Bio-Plex Pro™ TGF-β 3-plex Assay and double-beam laser analyzer Bio-Plex 200, Bio-Rad, USA. Three isoforms of TGF-β (TGF-β1, TGF-β2, TGF-β3) were simultaneously detected in AH.Results. The study revealed a significant increase of TGF-β isoforms concentrations in AH of the advanced POAG compared to AH of the group with uncomplicated cataract: TGF-β1 (3.1 times higher), TGF-β2 (1.4 times) and TGF-β3 (6.9 times). The following direct significant correlations were found: between TGF-β1 and TGF-β2 (r=0.41, p

The aim of our study was to perform an association analysis between MMP2, MMP3, MMP9, VEGF gene polymorphisms and development of non-proliferative diabetic retinopathy (DR) in the type 2 diabetic patients (DM).201 DM patients: 90 cases of DR and 111 subjects without DR features were included into the study. Polymorphic variants of MMP2 (rs2438650), MMP3 (rs3025058), MMP9 (rs3918242), and VEGF (rs699947 and rs3025039) genes were assayed. The genetic typing was carried out by restriction fragment length polymorphism and TaqMan methods.The analysis of complex genotypes at the five polymorphic positions has revealed some significant findings in positive and negatively incorporated complexes. Increased frequencies of MMP2-1306 CC genotype in the group of patients with “early” development of complication, and more frequent combination of high-level HbA1c with MMP2-1306CC and MMP9-1562CT genotypes were shown in DR patients. Computerassisted modelling with visual reconstruction of network interactions between the genotypes involved into the destruction events and angiogenesis, as well as altered HbA1с levels (an integral parameter of glycemia), has revealed some differences in structural and functional organization of gene-gene and gene- protein interactions between the groups of patients with DR versus those without this disorder. Сonclusion. A design of interactome biological networks based on transcription regulation and metabolic pathways, as well as their topological analysis allows to build and study interactions of genes and proteins, with reference to pathogenetic studies of DM2 complications aiming for development of approaches to personalized prevention and therapy in future times.

The purpose of the study was to search high-informative genetic criteria of the personalized forecast at presence of the earliest feebly marked of clinical attributes of organum visus pathology development.Material and methods. The results of immunogenotypic survey of 403 persons, among which 102 patients with age-related macular degeneration (AMD) and 90 patients with diabetic retinopathy (DR), 211 patients of similar gender and age as control groups of comparison are submitted. The analysis of regulation locus polymorphism TNFА (rs361525, rs1800629 and rs1800630), IL1B (rs1143627), IL4 (rs2243250), IL6 (rs1800795), IL10 (rs1800872, rs1800872) genes, vascular endothelial growth factor gene VEGF (rs3025039, rs699947), matrix metalloproteinases genes MMP (rs2438650, rs3025058, rs3918242) in this groups has been carried out.Results and discussion. Two groups of parameters have been shown through comparison of combined genetic attributes frequencies in comparable groups with/or absence AMD. One of these groups is distributed with primary frequency among patients with AMD whereas another is distributed only among elderly with absence of clinical and tool attributes of disease. On the contrary the significant prevalence of the attributes positively associated with the pathology development over negatively associated attributes has been revealed among DR. The revealed genetic attributes specify mainly inflammatory character of DR, as against AMD in which prevail degenerate and sclerogenic processes.Conclusion. Thus, the results of received genetic researches show an opportunity to personify predisposition of the significant part of elderly patients to development of ophthalmo-pathology microangiopathy or degenerate genesis with the purpose of realization of purposeful preventive actions.

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.

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 perform a comparative analysis of interleukins IL-8 and IL-1β concentration in the lacrimal fluid of patients after the Lasik and Femto-Lasik operations.Materials and methods. Clinical data are based on results of Lasik and Femto-Lasik procedures (excimer laser Technolas 217z100, femtosecond laser FEMTEC 520F). The study included 3 groups of patients: the group I – patients after Lasik, the group II – after Femto-Lasik, and a control group. Determination of the interleukins IL-8, IL-1β concentration in lacrimal fluid was performed using the commercial test systems (Сytokine Ltd. Company, St.-Petersburg) according to the instructions of the manufacturer.Results. There are no statistically significant differences between the groups I and II. Any authentic change in the level of all tested indices was not revealed. It is an evidence of the absence of a significantly more damaging action of the femtosecond laser compared to the formation of corneal flap using of a mechanical microkeratome.Conclusions. It is authentically defined that the immune response of cornea to a surgical trauma does not change essentially depending on a type of the Lasik or Femto-Lasik procedure. However the increase pro-inflammatory cytokines in the early postoperative period is noted.

Purpose. To measure concentrations of transforming growth factor-β1 (TGF-β1), matrix-metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in the lacrima of cataract patients with pseudoexfoliation syndrome (PEX). Material and methods. Determination of the concentrations of IL-6, TGF-β1 and MMP-9 in lacrima was performed by the immune-enzyme analysis method in 71 cataract patients (71 eyes) with pseudoexfoliation syndrome (PEX) aged from 50 to 92 years (76±0.91). Results. It was found a significant increase of the concentrations of IL-6, TGF-β1 and MMP-9 in lacrima of patients with PEX. Conclusions. Increase of IL-6 and MMP-9 level may play an important role in the PEX pathogenesis. These cytokines are involved in the development of «subclinical» inflammatory process and activate the processes of destruction and proliferation. TGF-β1 has significant proliferative and anti-inflammatory activity. Increase of TGF-β1 level activates the processes of fibrosis and may be one of the pathogenetic factors in the formation of pseudoexfoliation material.

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.

Purpose. To study the content of the transforming growth factorbeta 2 (TGF-β2), vascular endothelial growth factor (VEGF), pigment epithelium factor (PEDF) and several cytokines in the vitreous body in patients with proliferative diabetic retinopathy (PDR), to evaluate an activity of proliferative and immune-inflammatory process.Material and methods. Vitreous samples of patients with proliferative diabetic retinopathy and retinal detachment traction were examined as well as patients with traction retinal detachment without the PDR (control). Concentration of TGF- β 2, VEGF, PEDF MCP-1, interleukin 4, 6, 8, 10, 17A was determined by the ELISA method.Results. A reliable increase in the concentrations of pro-inflammatory cytokines IL-17A, IL-8, IL-6, MCP-1, anti-inflammatory cytokine IL-4, transforming growth factor-beta 2, vascular endothelial growth factor, factor of pigment epithelium and monocyte chematacticprotein-1 was detected in the vitreous of PDR patients.Conclusions. The findings indicate the existence of cytokine regulation violations in the PDR pathogenesis. It was noted that the activity of local inflammatory and proliferative processes was determined in the PDR pathogenesis. The revealed correlative relationships indicate interdependence of these processes. The detected reliable increase of monocyte chemotactic protein-1 in the vitreous of PDR patients, allows to make an assumption about its participation in the mechanisms of vascular proliferation.

The purpose of this study was to examine changes in indicators that reflect the activation of the humoral immune system, the severity of the destructive processes and autoimmune reactions in patients with neoplastic diseases of the uterus. The testing revealed significantly higher concentrations of IgA, the levels of circulating immune complexes and antibodies to antigens of native DNA. The findings suggest the importance of the activation of immune (autoimmune) reactions and destructive processes in pathogenetic mechanisms of development of uterine fibroids and cancer of the uterus.

Abstract. Patients with exacerbation of chronic herpesvirus infection were subjected to immunocorrection therapy. In the course of treatment, time-dependent correlations were found between the changes in production of IFNγ, IL-1β and IL-6, and initial level of IFNγ. The patients with high initial concentrations of IFNγ did also exhibit above-normal initial IL-1Β and IL-6 values, as compared to appropriate parameters for a sub-group with low IFNγ levels. In the course of immunocorrection with Echinacea, all the patients showed increase in IFNγ levels. However, due to initially low IFNγ values, its increase was more pronounced than in persons with high background levels of IFNγ. Dynamics of IL-1Β decrease and changes in IL-6 concentrations were more expressed in cases of higher initial levels of these cytokines. The alterations revealed for IFNγ, IL-1Β and IL-6 levels confirm that immunocorrection with Echinacea causes reduced intensity of inflammation and activation of antiviral immune response. (Med. Immunol., 2008, vol. 10, N 2-3, pp 283-290).

Abstract. In present work, we studied some interrelations between tobacco smoking and the processes of immune system stimulation in healthy blood donors. In our opinion, this issue is especially important for the big industrial center, with rather strong antigenic exposure of the organism. The levels of circulating immune complexes (CIC) were used as a marker index which reflects specific antigen-antibody interactions during inflammation. According to the results obtained, the majority of persons who have high CIC levels were tobacco smokers (53.76%). Moreover, the percentage of persons with high CIC content, like as the mean values of this index is increased proportionally to the duration of smoking. A mixture of tobacco smoke components seems to exert direct toxic effect upon various compartments of the immune system and causes local irritation of bronchial tree, thus producing local and systemic inflammatory reaction. It is, possibly, an additional factor which determines activation of immune system, with a background of adverse antropogenic exposures typical to industrial centers. The data obtained allow us to affirm a toxic action of tobacco smoke upon the organism of smokers, with development of inflammatory reactions that are displayed as increased CIC levels at preclinical stage.

Examine changes in the parameters reflecting the activation of humoral immune system, the severity of the destructive processesand autoimmune reactions in patients with endometrial cancer . The findings suggest that the significance of activation of autoimmune reac tions and destructive processes in pathogenetic mechanisms of development of malignant tumors of the corpus uteri.