interleukin-8 and Glaucoma

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 characterized by the death of retinal ganglion cells (RGCs) and visual field defects, and is a leading cause of blindness worldwide. Caffeic acid phenethyl ester (CAPE), a natural polyphenolic found in propolis from honeybee hives, can inhibit the activation of nuclear factor κ light‑chain‑enhancer of activated B cells (NF‑κB) and has therapeutic potential in inflammatory disease. The present study used a rat model of optic nerve crush (ONC) injury to investigate the effect of CAPE on glaucoma. The death of RGCs at day 14 was significantly reduced in CAPE‑treated animals compared with the non‑treated group according to Brn3a and TUNEL staining. In addition, CAPE decreased the severity of inflammation in the retina, reflected by the decreased expression of inflammatory cytokines, including interleukin (IL)‑8, IL‑6, inducible nitric oxide synthase, cycloooxygenase‑2, tumor necrosis factor‑α and chemokine C‑C ligand‑2, in CAPE‑treated rats. The hypertrophy of astrocytes and Müller cells (gliosis) caused by ONC was also found to be attenuated by CAPE, accompanied by the inhibition of NF‑κB signaling. Similarly, in vitro, CAPE suppressed the proliferation and migration of primary astrocytes induced by lipopolysaccharide, as well as the activation of NF‑κB. These results suggest that CAPE protected against RGC and attenuated inflammatory responses in a rat model of ONC by suppressing NF‑κB activation.

Topics: Animals; Astrocytes; Caffeic Acids; Cell Death; Cell Movement; Cell Nucleus; Cell Proliferation; Cell Survival; Chemokine CCL2; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Ependymoglial Cells; Glaucoma; Gliosis; In Situ Nick-End Labeling; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; NF-kappa B; Nitric Oxide Synthase Type II; Optic Nerve Injuries; Phenylethyl Alcohol; Rats; Rats, Sprague-Dawley; Retina; Retinal Ganglion Cells; Signal Transduction; Transcription Factor Brn-3A; Tumor Necrosis Factor-alpha

The goals of this study were to determine if oxidative stress on human trabecular meshwork (HTM) cells influences the stability of key mRNAs containing AU rich elements (AREs) known to be associated with glaucoma progression, and if the presence of topographic cue alters the stability of these mRNAs.. HTM cells were treated with 300 μM hydrogen peroxide (H(2)O(2)) for 1 hour in the presence of 5 μg/mL actinomycin D and compared with untreated cells. The selected mRNAs (IL-6, IL-8, myocilin, SPARC [secreted protein, acidic and rich in cysteine], matrix metalloproteinase [MMP]-3, and MMP-9) from the cells were analyzed by using relative quantitative PCR. Immunohistochemistry for Hu antigen R (HuR) was performed in addition to Western blots of HuR. HTM cells were also grown on topographically patterned surfaces, and IL-6 mRNA was analyzed by quantitative PCR.. H(2)O(2) increased IL-6 mRNA stability 0.145 (0.095-0.27) to 0.345 (0.2-0.48) (normalized ratio, median [interquartile range]) (n = 5), while IL-8 mRNA was increased from 0.565 (0.408-0.6) to 0.775 (0.486-0.873) (n = 5). These differences were statistically significant (P = 0.0313, for both IL-6 and IL-8; Wilcoxon signed-rank test). The mRNAs of myocilin, SPARC, and MMP-3, which do not have AREs, were more stable after actinomycin D treatment and were not altered with oxidation. Western blot and immunohistochemistry demonstrated that H(2)O(2) treatment induces the translocation of HuR from the nucleus to the cytoplasm. Nanopatterned surfaces did not alter IL-6 mRNA stability.. Oxidative stress stabilizes IL-6 and IL-8 mRNAs significantly. The decay of certain mRNAs associated with glaucoma may be altered in the trabecular meshwork of glaucoma patients.

Topics: Adolescent; Adult; Aged; Blotting, Western; Cells, Cultured; Cytoskeletal Proteins; Dactinomycin; Disease Progression; ELAV Proteins; Eye Proteins; Fluorescent Antibody Technique, Indirect; Glaucoma; Glycoproteins; Humans; Hydrogen Peroxide; Immunohistochemistry; Interleukin-6; Interleukin-8; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Microscopy, Confocal; Middle Aged; Osteonectin; Oxidative Stress; Real-Time Polymerase Chain Reaction; RNA, Messenger; Trabecular Meshwork; Young Adult

Topics: Aqueous Humor; Glaucoma; Helicobacter pylori; Humans; Immunoglobulin G; Interleukin-8; Intraocular Pressure; MAP Kinase Signaling System; Peptides; Pressure; Promoter Regions, Genetic; Reactive Oxygen Species

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