Резюме. В статье представлены результаты исследования субпопуляционного состава лимфоцитов периферической крови у пациентов с ранними стадиями возрастной макулярной дегенерации, здоровых людей пожилого возраста без офтальмопатологии (группа риска ВМД) в сравнении со здоровыми молодыми людьми (контролем). Выявлено повышение абсолютного и относительного (процентного) количества цитотоксических (СD3 + СD8 +) и дубль-позитивных Т-клеток (СD3 + СD4 + СD8 +), В-лимфоцитов (СD19 +), увеличение частоты их повышенного содержания в крови у пациентов с начальной и промежуточной стадиями ВМД и здоровых лиц старшего возраста в сравнении с «молодым» контролем, что позволяет думать о возможной роли сдвигов в содержании данных субпопуляций лимфоцитов в патогенезе ВМД.

Non-infectious uveitis is one of the main and insufficiently studied causes of disability and blindness in patients with immuno-inflammatory diseases. Uveitis associated with spondyloarthritis, Behcet’s disease, juvenile idiopathic arthritis, systemic sarcoidosis and Vogt-Koyanagi-Harada syndrome are described more often and better than others, but the pathogenesis of different variants of their course is not well understood. Also, there remains a need to study the clinical and pathogenetic features of uveitis in rare autoimmune inflammatory diseases. Despite the currently existing diagnostic and therapeutic schemes, further study of the pathogenesis of uveitis associated with immune-inflammatory diseases is required, the research of a personalized approach and an algorithm for joint multidisciplinary diagnosis by specialists in various fields. A deeper understanding of the specific pathogenetic mechanisms will reveal new possibilities in the treatment of patients with autoimmune uveitis. This article is devoted to the current clinical and differential diagnostic aspects, common features and distinctive features associated with various variants of the course of non-infectious uveitis in patients with immuno-inflammatory diseases.

Neurodegenerative ophthalmopathology is one of the main causes of irreversible blindness and disability in the world. In the pathogenesis of diseases of this group, more and more attention has recently been paid to the role of local inflammation caused by the activation of innate immunity and the mechanisms of its genetic regulation. In recent years, works have appeared in the field of experimental ophthalmology that have demonstrated the possibility of NLRP1, NLRP3 inflammasome complexes assembling when exposed to hyperglycemia, oxygen deprivation of retinal cells, as well as modeling compressive stress similar to that in glaucoma [15]. However, the mechanism of inflammasome involvement in the development of neurodegenerative eye diseases remains unclear. The aim of the study was to investigate the local expression of genes encoding proteins of the NLRP3 inflammasome complex (NLRP3, CASP-1) in an experimental model of retinal degeneration in rabbits. The studies were performed on samples of tissue complex (TC) of the retina/retinal pigment epithelium (RPE) (retina/RPE TC), isolated from the eyes of 14 New Zealand albino rabbits, in which degenerative retinal lesion was modeled by a single subretinal injection of 0.01 mL of 0.9% sodium chloride solution, and 7 healthy rabbits without eye damage. The formation of retinal degeneration was judged on the basis of changes in morphofunctional parameters obtained during specialized ophthalmological research methods (optical coherence tomography, fundus autofluorescence, electroretinography) at follow-up periods of 1, 3 and 6 months. The level of expression of NLRP3 and CASP-1 genes in the retina/RPE TC was evaluated by reverse transcription polymerase chain reaction (RT-PCR). According to the results of the study, a statistically significant increase in NLRP3 gene expression (p < 0.001) was noted in the retina/RPE TC of experimental animals, which may indicate the involvement of NLRP-3 inflammasome components in the development of neurodegenerative retinal lesions. At the same time, the expression of the gene encoding CASP-1 was detected only in the retina/RPE TC of experimental eyes and is probably due to local inflammatory mechanisms in the retinal tissue.The high level of NLRP3, CASP-1 mRNA, detected in all retina/RPE TC samples of experimental eyes at late stages of the experiment (3 and 6 months), allows us to assume the formation of mechanisms (for example, activated glial phenotype) that support inflammation in retinal tissue. This should be taken into account in actively developing transplantation methods for the treatment of retinal degeneration.

Behcet’s disease (BD) is a systemic autoinflammatory-autoimmune disease (chronic systemic vasculitis) of unknown etiology, almost 70% of patients develop uveitis. BD pathogenesis is complex, human herpesviruses (HHV) play an important role among infectious trigger factors. Ability of herpesviruses to modulate cytokine production and evade host’s immune response is known.Aim of the study was to assess the effect of Herpes simplex virus type 1, Herpes simplex virus type 2, Cytomegalovirus, Epstein-Barr virus on systemic levels of chemokines, pro- and anti-inflammatory cytokines in BD with and without uveitis. Serum samples were collected from 116 BD patients chronically infected with HHV and examined in ELISA-test for markers of HHV reactivation (IgG-antibodies to immediate early HSV antigens 1, 2 and CMV, early EBV antigen). Concentration of IL-1β, IFNγ, MCP-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, IL-18, TNFα, GMCSF, Eotaxin, GRO-α, IP-10, MIP-1α, MIP-1β, SDF-1α, RANTES detected in multiplex analysis. TGF-β1, TGF-β2 were measured in ELISA-test. Depending on presence and activity of uveitis 3 groups of patients with BD were identified: group 1 – active uveitis, group 2 – remission of uveitis, group 3 – BD without ocular manifestations. After serological study 2 subgroups were highlighted in each group: a) patients with antibody markers of reactivation of at least one HHV, b) patients chronically infected with HHV, without serological signs of reactivation. Mean level and detection rate of cytokines and chemokines in patients with active uveitis (1a, 1b) and in remission (2a, 2b) were compared with patients without eye damage (3a, 3b). Chronic HHV infection (subgroup “b”) was compared with reactivation (subgroup “a”). A significant increase of MCP-1/ CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, IP-10, SDF-1α chemokines in serum, as well as IFNγ, TGF-β1, and TGF-β2 was observed in patients with uveitis (regardless of their activity) and HHV reactivation compared to patients without uveitis. Our data indicate that systemic production of cytokines and chemokines in BD patients and uveitis could be affected by the activity of chronic herpesvirus infections, and the greatest changes are related to chemokines.

In the previous part of the review clinical and diagnostic aspects of some non-infectious uveitis in patients with immunoinflammatory diseases were discussed. In this part we proceed the discussion of ocular manifestations of a number of other immunoinflammatory conditions. In addition to uveitis associated with spondyloarthropathies, rheumatoid arthritis, Still’s disease, juvenile idiopathic arthritis and systemic sarcoidosis described in the previous part, ocular manifestations are also common in systemic vasculitis, systemic lupus erythematosus, Vogt—Koyanagi—Harada syndrome. Despite the numerous diagnostic schemes and therapy algorithms developed to date, much in the pathogenesis of uveitis associated with immuno-inflammatory diseases remains unclear. The need to develop personalized and multidisciplinary approaches for the treatment and diagnosis of non-infectious uveitis in numerous systemic immunoinflammatory diseases remains relevant. In-depth understanding of etiopathogenetic mechanisms of immunoinflammatory processes will allow to develop new approaches in the treatment of patients with uveitis.