Nitric oxide and tumour necrosis factor alpha in the process of pseudoexfoliation glaucoma.

AIM: To establish the role of nitric oxide (NO), ascorbic acid and tumour necrosis factor-α (TNF-α) in the pathogenesis of pseudoexfoliation glaucoma (XFG). METHODS: Our study included 120 patients who were referred for cataract surgery. All patients were divided into four groups according to clinical findings: XFG, early and late pseudoexfoliation syndrome (XFS), and cataract (without pseudoexfoliation). Serum and aqueous humour levels of the ascorbic acid, NO and TNF-α were measured. The concentrations of the ascorbic acid and NO were measured by an appropriate spectrophotometric method. Enzyme-linked immunosorbent assay (ELISA) was used to determine TNF-α level. RESULTS: Aqueous humour concentration of ascorbic acid was significantly lower in patients with late XFS (0.61±0.11 mmol/L) and XFG (0.48±0.15 mmol/L) compared to patients with early XFS (0.9±0.15 mmol/L) and cataract (1.16±0.22 mmol/L), while there was no difference in serum concentration in all examined groups. Aqueous humour concentration of NO was significantly higher in patients with XFG (77.7±11.4 µmol/L) compared to patients with early XFS (50.27±9.34 µmol/L) and cataract (49.77±7.1 µmol/L), while serum concentration was increased in the early stage of XFS (73.26±8.29 µmol/L). Aqueous humour level of proinflammatory cytokine TNF-α was increased in patients with XFS (early 460.04±18.32 pg/mL; late 502.42±53.23 pg/mL) and XFG (510.34±43.07 pg/mL), while there was no difference in serum level in all examined groups of patients. CONCLUSION: Reduced ascorbic acid and elevated NO and inflammation related cytokine TNF-α level in aqueous humour of the patients with developed XFG suggest that oxidative stress induces local inflammation.

Proinflammatory Cytokines Induce XFG Development.

PURPOSE: To reveal the roles of proinflammatory cytokines within the process of pseudoexfoliation (PEX) production. METHODS: Our study included 120 patients referred to cataract surgery (early and late stage of pseudoexfoliation syndrome (XFS), pseudoexfoliation glaucoma (XFG), and control group). Serum and humor levels of cytokines were measured in a sample with high sensitivity enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Our findings revealed that TNF-α and IL-17, overlooked by IL-6 action in the early stage and in the phase of glaucoma, played the main role in the inflammation activation in the tissue in the early and late stage of XFS and in XFG. CONCLUSIONS: Local conditions cause chronic inflammation in the eye, subsequently activating fibrotic process with fibrotic tissue deposits in the eye.

Galectin-3 deficiency accelerates high-fat diet-induced obesity and amplifies inflammation in adipose tissue and pancreatic islets.

Obesity-induced diabetes is associated with low-grade inflammation in adipose tissue and macrophage infiltration of islets. We show that ablation of galectin-3 (Gal-3), a galactoside-binding lectin, accelerates high-fat diet-induced obesity and diabetes. Obese LGALS3(-/-) mice have increased body weight, amount of total visceral adipose tissue (VAT), fasting blood glucose and insulin levels, homeostasis model assessment of insulin resistance, and markers of systemic inflammation compared with diet-matched wild-type (WT) animals. VAT of obese LGALS3(-/-) mice exhibited increased incidence of type 1 T and NKT lymphocytes and proinflammatory CD11c(+)CD11b(+) macrophages and decreased CD4(+)CD25(+)FoxP3(+) regulatory T cells and M2 macrophages. Pronounced mononuclear cell infiltrate, increased expression of NLRP3 inflammasome and interleukin-1ß (IL-1ß) in macrophages, and increased accumulation of advanced glycation end products (AGEs) and receptor for AGE (RAGE) expression were present in pancreatic islets of obese LGALS3(-/-) animals accompanied with elevated phosphorylated nuclear factor-κB (NF-κB) p65 and mature caspase-1 protein expression in pancreatic tissue and VAT. In vitro stimulation of LGALS3(-/-) peritoneal macrophages with lipopolysaccharide (LPS) and saturated fatty acid palmitate caused increased caspase-1-dependent IL-1ß production and increased phosphorylation of NF-κB p65 compared with WT cells. Transfection of LGALS3(-/-) macrophages with NLRP3 small interfering RNA attenuated IL-1ß production in response to palmitate and LPS plus palmitate. Obtained results suggest important protective roles for Gal-3 in obesity-induced inflammation and diabetes.