[Analysis of associations of undifferentiated connective tissue dysplasia with the development of primary open-angle glaucoma. Clinical and genetic aspects].

Mutations and polymorphisms of the genes whose products are involved in the formation of extracellular matrix components can lead to the development of specific changes in the connective tissue of the eye in primary open-angle glaucoma (POAG). Understanding the nature of connective tissue pathology and its manifestations at the system level contributes to the development of specific markers of early detection and a personalized approach to the prevention and treatment of POAG.

PURPOSE: To study the associations between systemic manifestations of undifferentiated connective tissue dysplasia (uCTD) and the development of POAG based on clinical and molecular genetic studies.

MATERIAL AND METHODS: The observational study was conducted in the period from 2008 to 2021 (12 full years) and included retrospective data analysis of up to 15 years. The study involved 60 people with «suspected glaucoma» diagnosis and burdened heredity, who were divided into groups according to the severity of phenotypic signs of uCTD (on the T.I. Kadurina scale), as well as 15 people with «glaucoma» diagnosis whose morphological and immunohistochemical studies of the sclera were analyzed retrospectively. The comparison group consisted of 64 relatively healthy individuals. All patients underwent clinical-anamnestic, molecular-genetic, standard and special ophthalmological studies.

RESULTS: Significant associations were revealed between the development of POAG, and the presence of clinical and phenotypic manifestations of uCTD, carriage of the GT genotype and the T allele of the rs8136803 ( TIMP3 ) polymorphism, the AG genotype and the A allele of the rs652438 polymorphism ( MMP12 ), the GA genotype and the A allele of the rs3825942 polymorphism ( LOXL1 ).

CONCLUSION: The specific features of preclinical morphofunctional changes and glaucoma progression can be determined by a hereditary predisposition to the pathology of the connective tissue of the eye. Testing of clinical-phenotypic and molecular-genetic signs of uCTD in patients with suspected glaucoma is promising in preclinical diagnosis, prognosis, and personalized approach to prevention and treatment.