Prooxidant–antioxidant balance, peroxide and catalase activity in the aqueous humour and serum of patients with exfoliation syndrome or exfoliative glaucoma

BACKGROUND: Oxidative stress plays an important role in the pathobiology of exfoliation syndrome (XFS) and exfoliative glaucoma (XFG). METHODS: We investigated the prooxidant-antioxidant balance (PAB) in aqueous humour and serum samples of 20 consecutive cases of XFS, 20 of XFG, and 20 age-matched controls, employing a recently described novel assay. The activity of catalase and the levels of (hydrogen) peroxide were also measured in these samples. RESULTS: There was no significant difference between the PAB in the aqueous humour of the XFS group (82.5 +/- 10 AU) and age-matched control patients (78.9 +/- 13.4 AU; p > 0.05). A significant shift of the PAB balance in favour of oxidants was detected in the XFG group (90.2 +/- 7.6 AU) compared with controls (p < 0.001). In the serum of patients with XFS (138.8 +/- 13.2 AU) and XFG (124.08 +/- 13.50 AU), PAB was significantly altered in favour of oxidants as compared to age-matched controls (114.9 +/- 9.91 AU); p < 0.001). Catalase activity in the aqueous from XFS (10.1 +/- 4.5 U/ml) and XFG (12.2 +/- 6 U/ml) patients was significantly lower than that measured in the normal aqueous (14.6 +/- 1.9 U/ml). Similarly, a significantly lower catalase activity was found in XFS (103 +/- 21.4 U/ml) and XFG (116 +/- 38 U/ml) serum samples compared with controls (189.6 +/- 84.3 U/ml). Finally, (hydrogen) peroxide concentration in aqueous and serum samples from patients with XFS (aqueous: 26.9 +/- 6.6 muM; serum: 41 +/- 10 muM) and XFG (aqueous: 21.7 +/- 7 muM; serum: 32 +/- 4 muM) were significantly higher than that of the controls (aqueous: 9.6 +/- 5.8 muM; serum: 24 +/- 9 muM; p < 0.001). CONCLUSIONS: These findings suggest that in XFS oxidative stress is counterbalanced in the aqueous, whereas the development of XFG is accompanied by a disruption of this balance in favour of oxidants.     

与近视和糖尿病视网膜病变相互作用相关的细胞因子的研究进展

研究发现高度近视对糖尿病视网膜病变的发展有保护作用,而糖尿病视网膜病变也一定程度影响近视的发展,但是其机制尚未研究明确.可能与眼轴拉长、视网膜血流动力学改变、相关细胞因子的变化等各种因素有关.细胞因子是参与糖尿病视网膜病变和近视的发病机制的关键因素.本文就与高度近视和糖尿病视网膜病变之间相互作用相关细胞因子的研究进展作出综述.     

Cytokines, fibrosis and the failure of glaucoma filtration surgery

Current therapies for the prevention of fibrosis after glaucoma filtering surgery can be effective but often produce unwanted side effects. An understanding of the cellular basis of the fibrotic reaction may lead to better treatments. Wound repair revolves around angiogenesis and the activation of fibroblasts by cytokines. These peptides, a number of which have been described, act together in intricately complicated networks to encourage fibroblast chemotaxis, proliferation and contractility, as well as to stimulate the production of glycosaminoglycans and collagen. Since interferons seem to inhibit many of these responses, they deserve further evaluation in the treatment of ocular fibrosis.     

Prediction of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma by Using Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio

Purpose: To assess the levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with pseudoexfoliation syndrome (PEX) and to compare the NLR and PLR results of patients with PEX, PEX glaucoma (PXG), and healthy controls.

Methods: In total, 34 patients with PEX, 29 patients with PXG, and 42 healthy subjects were enrolled in this retrospective study. Complete ophthalmologic examination and complete blood count measurements were performed of all subjects. Complete blood counts were performed within 2 h of blood collection.

Results: There was a significant difference in NLR between PEX and control groups (p = 0.012) and PXG and control groups (p = 0.003). Also, a significant difference was found in PLR values between control and PXG groups (p = 0.024).

Conclusions: Our study for the first time provides evidence that PLR and NLR may be useful for predicting the prognosis of PEX patients and progression to PXG.     

Cytokines and Biologics in non-infectious autoimmune uveitis: Bench to Bedside

Intraocular inflammatory eye disease is one of the important causes of ocular morbidity. Even though the prevalence of uveitis is less common in relation to diabetic retinopathy, glaucoma or age related macular degeneration, the complexity and heterogeneity of the disease makes it more unique. Putative uveitogenic retinal antigens incite innate immunity by the process of antigen mimicry and have been shown to be associated in patients with intraocular inflammatory disease by numerous experimental studies. Laboratory diagnostic tools to aid the etiologic association in intraocular inflammatory disease have evolved over the last two decades and we are entering into an era of molecular diagnostic tests. Sophisticated novel technologies such as multiplex bead assays to assess biological signatures have revolutionized the management of complex refractory uveitis. Nevertheless, there is still a long way to go to establish the causal relationship between these biomarkers and specific uveitic entities. Experimental studies have shown the supreme role of infliximab in the management of Behcet''s disease. Despite significant experimental and case control studies, the deficiency of randomized clinical trials using these biologic agents has handicapped us in exploring them as a front line therapy in severe refractory uveitis. Studies still need to answer the safety of these potentially life threatening drugs in a selected group of patients and determine when to commence and for how long the treatment has to be given. This review article covers some basic concepts of cytokines in uveitis and their potential application for therapy in refractory uveitis.     

The role of the cytokines in the pathogenesis of pseudoexfoliation syndrome

AIM: To examine the mechanism of the development of pseudoexfoliation (PSX) syndrome via both cytokine formation and endothelial vasorelaxing and growth factors that will provide us new therapeutic insights for the treatment.METHODS: This is a cross sectional study included two groups; Group 1:control patients with nuclear cataract (n=20, aged 51-80 years). Group 2:PSX patients with nuclear cataract (n=18, aged 50-90 years). Patients with other ophthalmic problems and systemic diseases were excluded. Vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and nitrotyrosine levels were determined through serum samples by Enzyme-linked immunosorbent assay (ELISA) method. Nitrite-nitrate levels were measured with photometric endpoint determination.RESULTS: There were no significant differences between the groups in terms of age, VEGF, IL-1β, nitrite-nitrate and nitrotyrosine. The significant results were the mean IL-6 levels that were higher in PSX group 2 (37.68±29.52 pg/mL) compared to that in control group 1 (15.32±10.08 pg/mL) (P<0.001).CONCLUSION: Several interacting and extending biochemical pathways may lead to the promotion of VEGF and IL-6 expressions. IL-6 which is the only altered marker in our study may indirectly cause an increase of vascular permeability and neovascularization. We suggest inflammation as a factor that can be involved in etiopathogenesis of PSX.     

CD40 Expressed in Endothelial Cells Promotes Upregulation of ICAM-1 But Not Pro-Inflammatory Cytokines,NOS2 and P2X7 in the Diabetic Retina

PurposeCD40 is an upstream inducer of inflammation in the diabetic retina. CD40 is upregulated in retinal endothelial cells in diabetes. The purpose of this study was to determine whether expression of CD40 in endothelial cells is sufficient to promote inflammatory responses in the retina of diabetic mice.MethodsTransgenic mice with CD40 expression restricted to endothelial cells (Trg-CD40 EC), transgenic control mice (Trg-Ctr), B6, and CD40^−/− mice were made diabetic using streptozotocin. Leukostasis was assessed using FITC-conjugated ConA. Pro-inflammatory molecule expression was examined by real-time PCR, immunohistochemistry, ELISA, or flow cytometry. Release of ATP was assessed by ATP bioluminescence.ResultsDiabetic B6 and Trg-CD40 EC mice exhibited increased retinal mRNA levels of ICAM-1, higher ICAM-1 expression in endothelial cells, and increased leukostasis. These responses were not detected in diabetic mice that lacked CD40 (CD40^−/− and Trg-Ctr). Diabetic B6 but not Trg-CD40 EC mice upregulated TNF-α, IL-1β, and NOS2 mRNA levels. CD40 stimulation in retinal endothelial cells upregulated ICAM-1 but not TNF-α, IL-1β, or NOS2. CD40 ligation did not trigger ATP release by retinal endothelial cells or pro-inflammatory cytokine production in bystander myeloid cells. In contrast to diabetic B6 mice, diabetic Trg-CD40 EC mice did not upregulate P2X₇ mRNA levels in the retina.ConclusionsEndothelial cell CD40 promotes ICAM-1 upregulation and leukostasis. In contrast, endothelial cell CD40 does not lead to pro-inflammatory cytokine and NOS2 upregulation likely because it does not activate purinergic-mediated pro-inflammatory molecule expression by myeloid cells or induce expression of these pro-inflammatory molecules in endothelial cells.