RESUMO
The lacrimal gland (LG) is a tubuloacinar exocrine gland composed of acinar, ductal, and myoepithelial cells. Three-dimensional distribution of acinar lobules, ducts, and myoepithelial cells is necessary for the effective functioning of the organ. LG is the main organ of immune surveillance of the ocular surface system. The embryogenesis of the gland is regulated by the interaction of genetic mechanisms, internal epigenetic (enzyme systems, hormones) and exogenous factors. There is no doubt that there is a clear genetic program for the implementation of the complex process of embryonic development. The mechanisms regulating LG organogenesis initiate the work of a huge number of structural oncogenes, transcription and growth factors, etc. Studying the expression and selective activity of regulatory genes during organ development, their participation in the differentiation of different cell types is a current trend at the nexus of clinical genetics, molecular biology, embryology and immunocytochemistry. Due to its relatively simple structure and accessibility, human LG is a suitable object for potential application in regenerative medicine. Development of a universal protocol for obtaining functional differentiated secretory epithelium of LG capable of expressing tissue-specific markers is an urgent task. Determining the nature and origin of stem cells and progenitor cells will allow the isolation and multiplication of these cells in culture. After obtaining a functionally active culture of LG cells, it is possible to create a model of autoimmune diseases.
Assuntos
Doenças do Aparelho Lacrimal , Aparelho Lacrimal , Medicina Regenerativa , Humanos , Medicina Regenerativa/métodos , Aparelho Lacrimal/embriologia , Aparelho Lacrimal/fisiologia , Doenças do Aparelho Lacrimal/terapia , Doenças do Aparelho Lacrimal/fisiopatologia , Diferenciação Celular/fisiologiaRESUMO
One of the etiological causes of dry eye disease (DED) is systemic autoimmune diseases (AID): primary Sjögren's syndrome (PSS), rheumatoid arthritis (RA); their manifestation may begin with ophthalmic symptoms. The relationship of PSS and RA with genetic factors is proven. The contribution of polymorphic markers of the genes THBS1, MUC1, TRIM21, STAT4, PTPN22 in the development of these diseases is established, as well as their connection with the development of DED. A panel of genetic markers for evaluating the risk of developing DED in PSS and RA is developed, and its sensitivity and specificity is determined. PURPOSE: The aim of the study was to determine the prognostic significance of a panel of polymorphic gene markers in the development of dry eye syndrome in patients with primary Sjögren's syndrome and rheumatoid arthritis over a five-year follow-up period. MATERIAL AND METHODS: Patients with a verified diagnosis of PSS and RA without signs of DED were examined (n=35 and n=42, respectively). The control group included 82 volunteers without AID and DED. The observation period was 5 years. Every year all study subjects underwent an ophthalmological clinical and functional examination. RESULTS: Dry eye disease had developed in groups of patients with AID with predisposing genotypes of polymorphic markers of the genes THBS1, MUC1, TRIM21, STAT4, PTPN22. The peak of DED development in these patients was in the third year of the follow-up. As a result of ROC analysis, it was found that the sensitivity and specificity of determining the predisposing genotypes of polymorphic markers of the THBS1, MUC1, TRIM21, STAT4, PTPN22 genes was 68 and 87%, respectively (p<0.0001). CONCLUSION: Genetic research methods are essential for minimally invasive early diagnosis of dry eye disease, and can subsequently become the basis for a personalized approach to its treatment.