Investigation of the effect of TNF-α on damage to retinal pigment epithelial cells in age-related macular degeneration

Abstract

Oxidative stress alters cellular homeostasis and elicits a cellular response that depends on the severity and type of damage: some cells activate defense mechanisms designed to ensure survival; the other, provided that the defense mechanisms are inhibited, triggers alternative signaling pathways that lead to apoptosis, necrosis, pyroptosis, autophagy, and so on. However, the exact cause of such damage and induction of oxidative stress, including the associated oxidative effects around pigment epithelial cells in the context of the onset and progression of age-related macular degeneration – one of the world’s most common eye diseases with blindness, remains unclear. Therefore, in the course of the study we turned to key biogenetic points of regulation of inflammation and apoptosis, in particular TNF. The aim of the work is to shed light on the role of TNF as a genetic determinant that can initiate and influence the course of age-related macular degeneration. For this purpose, the main pathognomonic markers of the morphological structure of the macula were determined in 291 persons with age-related macular degeneration and in 105 persons without ophthalmic pathology, using optical coherence tomography to confirm or exclude the diagnosis of the disease. To detect polymorphism of the TNF gene, we used the method of real-time PCR diagnostics on the BioRad CFX 96 amplifier using LiTech reagents. Statistical processing of the results was performed using Hardy-Weinberg equilibrium, Kruskal-Wallis method, logistic regression analysis and construction of the ROC curve to determine the AUC range and sensitivity and specificity values. The study revealed a significant difference in the distribution of mutant genotypes between patients with both forms of AMD and the control group. There was also a statistically significant effect of mutant allele A on the development of both "dry" (OR = 3.40; 95.0 %; CI = 1.90-6.07, p<0.001) and "wet" form of AMD (OR = 4.78; 95.0 % CI 2.65-8.64, p<0.001), and in the analysis of mutant genotypes it was found that the GA genotype increases the chances of "dry" and "wet" forms of the disease by 3.13 and 4.74 times, respectively, while AA – 5 times, regardless of the form of the disease. confirms the influence of TNF gene polymorphism on the occurrence and progression of age-related macular degeneration. In the analysis of ROC-curves and AUC regions, it was found that all mutant genotypes have a significant effect on the occurrence of age-related macular degeneration (p<0.05). However, the obtained values of sensitivity and specificity, especially in the AA genotype in both "dry" (17.9 % and 95.8 %, respectively) and "wet" (18.2 % and 95.8 %, respectively) forms of age-related macular degeneration indicate a low chance of error-free confirmation of the diagnosis. a disease that may be associated with multifactorial disease and requires further research.