Komparativna analiza genske varijabilnosti i nivoa cirkulišućih faktora nekroze tumora, HSP 70 i Fas/FasL u primarnom glaukomu otvorenog ugla

Abstract

Genetic heterogeneity of primary open-angle glaucoma, and concentration changes of various inflammation and immune response mediators in the blood, aqueous humor or tissues, indicate the involvement of different genetic mechanisms and immune system activity in the pathogenesis of POAG. The aim of study was to determine the interdependent clinical, genetic and biochemical findings in POAG-HTG patients. Distribution of genetic polymorphisms for TNF-α -308 G/A and - 863 C/A in DNA samples was examined using PCR-RFLP, the concentrations of circulating TNF-α and HSP 70 in a plasma and concentration of sFas and sFasL in the aqueous humor were measured by commercial ELISA tests. Their association with quantitative clinical parameters was examined. This study included 357 subjects: 81 POAG-HTG, 35 PEXG, 77 with senile cataract and 164 healthy subjects age-sex matched. Furthermore, 35 samples of aqueous humor of POAG-HTG patients , 24 PEXG and 29 with senile cataract were treated. The results showed that serum concentration of TNF-α was significantly higher in patients with glaucoma. Genotypes GG TNF-α (-308) and CC TNF-α (-863) were significantly higher in POAGHTG. No significant association between TNF-α (-308) G/A and TNF-α (-863) C/A polymorphism and investigated clinical parameters was found in POAG-HTG. HSP 70 concentration significantly affects MD, RNFL Avg, Sup and Inf in POAG-HTG patients. There is a significant negative correlation between Fas concentration and RNFL Inf, and negative correlation of FasL with MD and RNFL Avg in POAG-HTG. The study concluded that serum TNF-α is a powerful cytokine with potent significant role in the pathogenesis of glaucoma and glaucoma neuropathy. HSP 70, sFas and sFasL play a role in pathogenesis of POAG and may be indicators of the development and progression of glaucoma neuropathy. It has been shown that TNF-α (- 863) A allelic polymorphism has a protective role in the pathogenesis of POAG.