interleukin-8 and Glaucoma--Open-Angle

To estimate an accurate level of IL-8 in aqueous humor among open-angle glaucoma (OAG) patients.. Meta-analysis was performed from available studies that investigated the IL-8 level in the aqueous humor of OAG patients and control subjects.. A total of 17 studies were selected. The pooled result showed that IL-8 levels in aqueous humor of patients with OAG were higher than in control subjects (SMD=0.98, 95% CI=0.68-1.27, p<0.00001).. This meta-analysis indicates that patients with OAG may have a higher aqueous humor IL-8 levels compared to control subjects, which supports the notion that IL-8 is one of the contributing factors in the development of OAG.

Topics: Aqueous Humor; Glaucoma, Open-Angle; Humans; Interleukin-8

Exfoliation syndrome (XFS) produces deleterious ocular aging and has protean systemic manifestations. Local ocular production of TGFβ1 is of central importance in XFS. TGFβ1 appears to induce the expression of LOXL1 and the production of other extracellular matrix components which are known to be present in exfoliation material. Furthermore, results from several studies find that the aqueous humor of exfoliation glaucoma patients exhibits a decreased antioxidant defense and increased oxidative stress systems. Finally, studies show that the levels of interleukin-6 and interleukin-8 in the aqueous humor of XFS patients were 3-fold higher than in controls. Overall TGFβ1, as well as a prooxidative and proinflammatory environment seems to play an important role in XFS.

Topics: Amino Acid Oxidoreductases; Aqueous Humor; Exfoliation Syndrome; Extracellular Matrix; Glaucoma, Open-Angle; Humans; Inflammation; Interleukin-6; Interleukin-8; Intraocular Pressure; Oxidative Stress; Transforming Growth Factor beta1

The aim of the study was to assess the influence of different regimes of patient's preparation before trabeculectomy on the markers of healing process in Tenon's fibroblast cultures.The studied group consisted of 66 patients with open angle glaucoma undergoing primary trabeculectomy. The patients were divided into 5 groups with different regimes of preparation before the surgery based on application or withdrawal of topical antiglaucoma medications and steroids (G1-patients using antiglaucoma drops until the day of the surgery; G2-patients using antiglaucoma drops until the day of the surgery and additionally dexamethasone for 4 weeks before surgery; G3-patients who stopped using antiglaucoma drops 4 weeks before the surgery and introduced dexamethasone for 4 weeks before surgery; G4-patients who stopped using antiglaucoma drops 4 weeks before the surgery; G5-control group, patients with newly diagnosed glaucoma in whom trabeculectomy was the first treatment option without medical treatment). During trabeculectomy the samples of Tenon's capsule were obtained. Tenon fibroblasts were isolated directly from the explants to test their proliferation ability and the level of released healing markers. Following factors typical of healing process were evaluated using commercially available ELISA kits: IL 1-β, IL-6, IL-8, VEGF-A, TGF-β1 and MMP-9. Concentrations of IL-1β, IL-6 and TGF-β1 were significantly higher in the group obtaining antiglaucoma drops. Additionally, in this group the fibroblasts revealed the highest proliferation potential, indicating the active healing process. The levels of IL-8, VEGF-A and MMP-9 were similar between the groups. Our study shows that for the best conjunctival anti-inflammatory control, the most influential factor is the withdrawal of antiglaucoma medications.

Topics: Antiglaucoma Agents; Cells, Cultured; Conjunctiva; Dexamethasone; Fibroblasts; Glaucoma, Open-Angle; Humans; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 9; Trabeculectomy; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A

To compare the concentrations of protein markers in aqueous humor (AH) of patients with primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), acute primary angle closure (APAC), and cataract without glaucoma as the control group. AH samples were collected at the beginning of surgery from 82 eyes of 82 patients who were divided into POAG (n = 23), CACG (n = 21), APAC (n = 19), and cataract groups (n = 19). The expression levels of interferon-gamma (IFN-γ), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17A (IL-17A), lymphotoxin-alpha (LT-α), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), brain derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-AA (PDGF-AA), vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), and tumor necrosis factor-alpha (TNF-α) in AH were detected using a microsphere-based immunoassay. The AH levels of TNF-α, MMP-2, MCP-1, IFN-γ, and TIMP-1 in the APAC and CACG groups were significantly higher than those in control eyes. Additionally, the AH levels of interleukin-6 (IL-6) and VEGF in the APAC group were significantly higher than those in the control group (CG). The interleukin-8 (IL-8) levels in patients with POAG were significantly higher than those in control eyes, whereas the LT-α levels were significantly lower than those in control eyes. IL-6 levels were significantly correlated with the coefficient of variation (CV), whereas IL-6 levels were significantly negatively correlated with the frequency of hexagonal cells (HEX) and corneal endothelial cell density (CD). The levels of TNF-α, MMP-2, MCP-1, IFN-γ, TIMP-1, IL-6, IL-8, VEGF, and LT-α were different among the three types of glaucoma. These different types of glaucoma may be caused by various pathogeneses, which opens avenues for further investigation into the pathogenesis of glaucoma and discoveries new targets and pathways for the treatment of glaucoma.

Topics: Aqueous Humor; Brain-Derived Neurotrophic Factor; Cataract; Chemokine CCL2; Cytokines; Fibroblast Growth Factor 2; Glaucoma; Glaucoma, Open-Angle; Humans; Interferon-gamma; Interleukin-17; Interleukin-2; Interleukin-6; Interleukin-8; Lymphotoxin-alpha; Matrix Metalloproteinase 2; Platelet-Derived Growth Factor; Tissue Inhibitor of Metalloproteinase-1; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Glaucoma is a leading cause of blindness worldwide. Purpose of this study was to identify molecular markers that were significantly correlated with presence of glaucoma and outcome of glaucoma surgery. To accomplish this, we determined the profiles of pro-inflammatory cytokines in the aqueous humor of 101 glaucoma patients; 31 primary open angle glaucoma (POAG), 38 pseudoexfoliation glaucoma (PEG), and 32 neovascular glaucoma (NVG). We also studied 100 normal subjects as controls. In eyes with POAG or PEG, the level of interleukin (IL)-1α, IL-2, IL-4, IL-8, IL-23, and CCL2 were significantly elevated. In the NVG eyes, many inflammatory cytokines were also highly elevated. IL-8 had the highest odds ratio, and levels of IL-8 and CCL2 were significantly correlated with preoperative IOP or visual field defects in PEG eyes. Principal component analysis showed that IL-8 had the highest association to the IOP-cytokine component, and Cox proportional hazard model indicated that an elevation of IL-8 was a significant risk of filtering surgery failure. Together with modeling of their interactions and prognosis, IL-8 elevation is a significant risk factor both for detecting and managing glaucoma and may serve as a therapeutic target candidate to improve the prognosis of glaucoma surgery.

Topics: Aged; Aqueous Humor; Female; Glaucoma, Neovascular; Glaucoma, Open-Angle; Humans; Interleukin-8; Male; Prognosis

To investigate latent conjunctival Chlamydia trachomatis (CT) and Bacteroides fragilis (BF) infections as potential risk factors for posttrabeculectomy bleb failure.. This retrospective observational study included 50 primary open-angle glaucoma eyes of 50 patients who were submitted to trabeculectomy without cytostatics from September 2010 to June 2011 and were followed up for at least a year. Preoperatively, conjunctival scrapings were taken and their specimens subjected to polymerase chain reaction, direct fluorescent assay and cell culture testing for CT, and culture for BF on blood agar medium. Serum CT-specific IgG and IgA and tear interleukin (IL)-1β and IL-8 concentrations were measured with enzyme-linked immunosorbent assay. We defined bleb failure as intraocular pressure >21 mm Hg with antiglaucoma medications, resulting from reduced bleb filtration capacity due to bleb fibrosis, fistula obstruction, flattened bleb, or encapsulated bleb, and no earlier than 2 weeks after surgery. At the time of the reintervention, a scleroconjunctival biopsy was obtained for histopathology (including direct fluorescent assay testing for CT). Eyes were divided into a failure group and a nonfailure group, depending on whether they developed bleb failure (required reintervention) or not within a follow-up year.. In the failure group (n=18), the frequencies of detection of CT and BF in conjunctival specimens were 27.8% and 66.7%, respectively, versus 0% and 9.4% in the nonfailure group (n=32). CT and BF were detected in 11.1% and 11.1%, respectively, of scleroconjunctival biopsies. IgG and IgA seropositivity to CT was found in 66.7% and 33.3%, respectively, of the failure group patients, versus 9.4% and 0% of the nonfailure group patients. Tear IL-1β and IL-8 levels were markedly elevated in the failure group (468.83±80.43 and 107.89±15.11 pg/mL, respectively) versus the nonfailure group (22.34±5.43 and 9.34±2.83 pg/mL, respectively).. Being a contributor to low-grade conjunctival inflammation, latent conjunctival CT, and BF infections in primary open-angle glaucoma patients represent risk factors for posttrabeculectomy bleb failure.

Topics: Aged; Antibodies, Bacterial; Bacteroides fragilis; Bacteroides Infections; Chlamydia Infections; Chlamydia trachomatis; Conjunctivitis, Bacterial; Eye Infections, Bacterial; Eye Proteins; Female; Fluorescent Antibody Technique, Direct; Glaucoma, Open-Angle; Humans; Immunoglobulin A; Immunoglobulin G; Interleukin-1beta; Interleukin-8; Intraocular Pressure; Male; Middle Aged; Polymerase Chain Reaction; Postoperative Complications; Retrospective Studies; Risk Factors; Tears; Tonometry, Ocular; Trabeculectomy; Treatment Failure

To analyze the effects of factors on aqueous humor proinflammatory cytokine and growth factor levels in patients with uveitic glaucoma (UG).. In this cross-sectional study, we enrolled 143 participants: 1) UG patients (n = 39); 2) primary open-angle glaucoma (POAG) patients (n = 36); and 3) cataract surgery patients, as a comparative group (n = 68). Aqueous humor samples were obtained at the start of surgery. Aqueous cytokine levels were determined using a multiplex immunoassay (xMAP and the Human Cytokine/Chemokine Panel I).. In UG cases, mean interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-α, platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB, and VEGF levels were 171.1, 214.5, 2791.7, 3.5, 23.9, 5.4, and 168.9 pg/mL, respectively, and were higher than those in cataract (non-glaucomatous) cases except PDGF. Levels of IL-6, MCP-1, and VEGF were higher in UG cases than in POAG cases. UG cases with a history of phacoemulsification displayed significantly higher levels of IL-6 (P = 0.0164), IL-8 (P = 0.0003), MCP-1 (P = 0.0465), and PDGF-AB/BB (P = 0.0062) compared to the phakic cases. The presence of cells in the anterior chamber was related to higher levels of IL-8 (P = 0.0002), TNF-α (P = 0.0037), and PDGF-AB/BB (P = 0.0009). The level of PDGF-AB/BB was higher in infectious uveitis than in non-infectious uveitis (P = 0.0211). The level of transforming growth factor (TGF)-β2 was negatively correlated with the levels of MCP-1 (adjusted R2 = 0.28, t = -2.45, P = 0.031) and TNF-α (adjusted R2 = 0.27, t = -2.43, P = 0.032).. A history of phacoemulsification, the presence of cells in the anterior chamber, and infectious uveitis were related to aqueous proinflammatory cytokine levels in patients with UG. TGF-β2 might be an anti-inflammatory factor in aqueous humor of UG patients.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Aqueous Humor; Chemokine CCL2; Cross-Sectional Studies; Cytokines; Female; Glaucoma, Open-Angle; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Vascular Endothelial Growth Factor A

Pseudoexfoliation (PEX) syndrome, which is an age-related, generalized elastotic matrix process, currently represents the most common identifiable risk factor for open-angle glaucoma. Dysregulated expression of proinflammatory cytokines has been implicated in the initiation of various fibrotic disorders and in the pathophysiology of glaucoma. Here we investigated the presence, expression, regulation, and functional significance of proinflammatory cytokines in eyes with early and late stages of PEX syndrome/glaucoma in comparison with normal and glaucomatous control eyes using multiplex bead analysis, immunoassays, real-time PCR, Western blotting, immunohistochemistry, and cell culture models. Early stages of PEX syndrome were characterized by approximately threefold (P < 0.005) elevated interleukin (IL)-6 and IL-8 levels in the aqueous humor and a concomitant approximately twofold (P < 0.001) increase in mRNA expression levels in anterior segment tissues as compared with controls. In contrast, late stages of PEX syndrome/glaucoma did not differ significantly from controls. IL-6, IL-6 receptor, and phospho-signal transducer and activator of transcription 3 could be mainly localized to walls of iris vessels and to the nonpigmented epithelium of ciliary processes. IL-6 and IL-8 were significantly up-regulated by ciliary epithelial cells in response to hypoxia or oxidative stress in vitro, whereas IL-6, but not IL-8, induced the expression of transforming growth factor-beta1 and elastic fiber proteins. These findings support a role for a stress-induced, spatially, and temporally restricted subclinical inflammation in the onset of the fibrotic matrix process characteristic of PEX syndrome/glaucoma.

Topics: Adult; Aged; Aged, 80 and over; Animals; Aqueous Humor; Cell Line; Cytokines; Exfoliation Syndrome; Extracellular Matrix; Eye; Female; Glaucoma, Open-Angle; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Molecular Sequence Data

To test the hypothesis that immune activation occurs in glaucoma by comparing concentrations of multiple cytokines in aqueous humor (AH) from patients with primary open angle glaucoma (POAG) and from cataract patients without glaucoma as controls.. Cytokine concentrations in AH obtained during surgery were measured using microparticle-based immunoassays. Localized expression of IL-8 protein was investigated by immunohistochemistry of human eyes.. Eight cytokines (IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12, IFN-γ, and TNF-α) were below the limits of detection, and two cytokines (IL-18 and IL-15) were detected at low levels or in only a few patients. Although IL-6 was detected in 26 of 30 control patients (median, 2.7 pg/mL) and in 23 of 29 POAG patients (median, 1.6 pg/mL), the difference was not statistically significant. IL-8 was detected in 28 of 30 control patients (median, 1.8 pg/mL) and in all 29 POAG patients (median, 4.9 pg/mL). The higher IL-8 concentration in the AH of POAG patients was statistically significant (P < 0.001). In pairs of eyes from patients with asymmetric glaucomatous optic nerve damage, IL-8 concentration was higher in the AH of the more severely affected eye (P < 0.05). Patients with severe visual field defects had higher IL-8 concentrations in the AH than did patients with mild visual field defects. IL-8 protein expression was found in human retina and optic nerve.. Concentration of the inflammatory cytokine IL-8 is significantly elevated in the AH of POAG patients, supporting the hypothesis that immune activation occurs in glaucoma.

Topics: Aged; Aged, 80 and over; Aqueous Humor; Cataract; Female; Glaucoma, Open-Angle; Humans; Immunoassay; Interleukin-8; Male; Middle Aged; Optic Nerve Diseases; Tomography, Optical Coherence; Vision Disorders; Visual Fields

To investigate the expression of three inflammation markers, HLA-DR, IL-6, and IL-8, by conjunctival epithelial cells obtained using impression cytology (IC) samples from long-term treated glaucoma patients.. IC samples were obtained from the 60 following individuals: 45 patients suffering from primary open-angle glaucoma and receiving topical treatments for at least 1 year and 15 subjects with no ophthalmological disease (controls). Membrane expression of HLA-DR and intracellular expression of IL-6 and IL-8 were quantified, respectively, by indirect and direct immunofluorescence techniques. Fluorescence levels were quantified using calibrated fluorescent beads.. The percentage of HLA-DR-positive cells was significantly higher on IC samples from multitreated glaucoma patients and from patients treated by either preserved betablocker or preserved prostaglandin analogue than on IC samples from control individuals. Interestingly, the percentage of HLA-DR-positive cells was not significantly increased upon treatment with unpreserved betablocker. However, the percentage of IL-6- and IL-8-positive cells as well as IL-6 and IL-8 expression levels was significantly higher in patients than in controls, regardless of the treatment type and the presence of preservative. A significant positive correlation was found between HLA-DR and cytoplasmic IL-6 expression, between HLA-DR and cytoplasmic IL-8 as well as between IL-6 and IL-8 cytoplasmic expressions.. The present study confirms that there is an increased expression of HLA-DR in treated glaucoma patients compared to controls and demonstrates that antiglaucoma treatments lead to increased IL-6 and IL-8 expressions. It also indicates that benzalkonium-preserved eyedrops and preserved multitherapy may induce stronger inflammatory responses than do unpreserved eyedrops, although further studies are needed to determine the respective inflammatory role of preservative and therapeutic molecules. In this study, flow cytometry was used to detect the intracellular pro-inflammatory cytokines in conjunctival cells obtained by impression cytology. This standardized and reliable technique was a useful tool to assess inflammatory and allergic ocular surface disorders.

Topics: Adrenergic beta-Antagonists; Benzalkonium Compounds; Carbonic Anhydrase Inhibitors; Conjunctiva; Cytological Techniques; Cytoplasm; Data Interpretation, Statistical; Epithelial Cells; Female; Flow Cytometry; Fluorescent Antibody Technique, Direct; Fluorescent Antibody Technique, Indirect; Glaucoma; Glaucoma, Open-Angle; HLA-DR Antigens; Humans; Interleukin-6; Interleukin-8; Male; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins; Time Factors