interleukin-8 and Wet-Macular-Degeneration

To clarify the association between IL-8 gene polymorphisms, IL-8 level, towards the risk of age-related macular degeneration (AMD).. Meta-analysis was performed from available studies that investigated IL-8 -251A/T (rs4073) and +781C/T (rs2227306) polymorphisms and IL-8 levels in patients with AMD and controls.. Overall, the pooled result showed a significant association between AMD with allelic (T vs. C; OR 1.53; p = 0.005), dominant (TT + CT vs. CC; OR 1.95; p = 0.017), homozygous (TT vs. CC; OR 2.03; p = 0.039) and heterozygous (CT vs. CC; OR 1.92; p = 0.032) models of rs2227306; while subgroup analysis revealed a significant association between rs2227306 with wet AMD in allelic (T vs. C; OR 1.69; p = 0.016), recessive (TT vs. CT + CC; OR 1.81; p = 0.00007), and homozygous (TT vs. CC; OR 2.64; p = 0.003) models. No significant association was observed between rs4073 with AMD in all inheritance models. In parallel, patients with AMD, particularly wet AMD had an elevated level of IL-8 compared to control.. This meta-analysis suggests that patients with AMD or wet AMD have higher IL-8 levels compared to control, which is also supported by the evidence that carrier T allele of rs2227306 exhibited an increase in the risk of AMD or wet AMD. Thus, IL-8 +781C/T (rs2227306) polymorphism and the level of intraocular IL-8 may be useful as a biomarker for early detection and a therapeutic target of AMD.

Topics: Alleles; Homozygote; Humans; Interleukin-8; Polymorphism, Single Nucleotide; Wet Macular Degeneration

It has been hypothesized that epithelial-mesenchymal transition (EMT) may occur in the retinal pigment epithelium of advanced stage age-related macular degeneration (AMD). Various serum and plasma growth factors and inflammatory mediators have been linked to AMD. We were interested in finding out whether systemic levels of EMT-associated markers were altered in the serum of wet AMD patients. Serum biomarkers associated with the various pathological processes of AMD may present an avenue towards identifying and characterizing the birth mechanisms of wet AMD, its progression and severity, paving the way towards the application of precision medicine.. We chose to measure the serum levels of known biomarkers of EMT - EGF (epidermal growth factor), ET-1 (endothelin 1), IL-8 (interleukin 8), TGF-β1 and TGF-β2 (transforming growth factor-beta 1 and 2) and VEGF-A (vascular endothelial growth factor A) - using enzyme-linked immunosorbent assays. We measured them from 71 Finnish wet AMD patients who were receiving intravitreal anti-VEGF-A injection treatments, as well as 64 age-adjusted controls.. We found significantly elevated levels of ET-1, IL-8 and TGF-β2 in the serums of wet AMD patients.. ET-1, IL-8 and TGF-β2 appear to be useful serum biomarkers in understanding active wet AMD. However, we cannot conclude that local retinal EMT-processes could be observed from the corresponding systemic serum biomarkers in patients undergoing anti-VEGF-A treatments.

Topics: Biomarkers; Epithelial-Mesenchymal Transition; Finland; Humans; Interleukin-8; Transforming Growth Factor beta2; Vascular Endothelial Growth Factor A; Wet Macular Degeneration

Systemic levels of pro-inflammatory cytokines and activated complement components affect the risk and/or progression of neovascular age-related macular degeneration (AMD). This study investigated the effect of serum pro-inflammatory cytokine levels and complement pathway activity on the clinical response to vascular endothelial growth factor (VEGF) inhibition in neovascular AMD.. Sixty-five patients with a new diagnosis of neovascular AMD were observed over a six-month period in a single-centre, longitudinal cohort study. At each visit, the visual acuity score (VAS), central macular thickness (CMT), serum levels of CRP, pro-inflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6 and IL-8), and complement pathway activity were measured. Participant DNA samples were sequenced for six complement pathway single nucleotide polymorphisms (SNPs) associated with AMD.. A statistically significant difference in VAS was observed for serum levels of TNF-α only: there was a gain in VAS (from baseline) of 1.37 for participants below the 1st quartile of mean concentration compared to a reduction of 2.71 for those above the 3rd quartile. Statistical significance was maintained after Bonferroni correction (P value set at <0.006). No significant differences in CMT were observed. In addition, statistically significant differences, maintained after Bonferroni correction, were observed in serum complement activity for participants with the following SNPs: CFH region (rs1061170), SERPING1 (rs2511989) and CFB (rs641153). Serum complement pathway components did not significantly affect VAS.. Lower serum TNF-α levels were associated with an increase in visual acuity after anti-VEGF therapy. This suggests that targeting pro-inflammatory cytokines may augment treatment for neovascular AMD.

Topics: Angiogenesis Inhibitors; Complement C1 Inhibitor Protein; Complement Factor H; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Longitudinal Studies; Polymorphism, Single Nucleotide; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration

Topics: Case-Control Studies; China; Complement Factor I; Gene Frequency; Genotype; Humans; Interleukin-8; Polymorphism, Single Nucleotide; Receptors, Transferrin; Transferrin; Wet Macular Degeneration

Geographic atrophy (GA) is a clinical phenotype of late age-related macular degeneration (AMD) with no current treatment available. In this study, we investigated markers of chronic inflammation in plasma of patients with GA and how these relate to progression rate.. We prospectively included 42 patients with GA, 41 patients with neovascular AMD, and 27 healthy controls. We quantified levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF) receptor 2, and C-reactive protein (CRP). We adapted an inflammation summary score to cluster conceptually related markers of chronic inflammation. Enlargement rate of the atrophic lesion was measured from fundus autofluorescence images performed at baseline and after 1 year.. Patients with GA showed an increase in proinflammatory markers of IL-6 (P = 0.009), TNF receptor 2 (P = 0.013), and CRP (P = 0.017) compared to healthy controls. We found that IL-8 levels were markedly higher in patients with GA when compared to patients with neovascular AMD (P = 0.013). The inflammation summary score was high in patients with neovascular AMD (P = 0.024), but even higher in patients with GA (<0.001), when compared to healthy controls. GA enlargement was measured in 36 patients, who completed follow-up. Plasma levels of IL-6 had a moderate but significant correlation with GA enlargement rate (R2 = 0.23, P = 0.0035).. Markers of chronic inflammation strongly associates with presence of GA secondary to AMD. Plasma IL-6 possesses predictive ability of progression and constitutes the first known plasma biomarker of disease activity in GA. These findings shed light into a poorly understood clinical phenotype of AMD and highlights the important role of chronic inflammation in GA.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Disease Progression; Female; Fluorescein Angiography; Genotyping Techniques; Geographic Atrophy; Humans; Interleukin-6; Interleukin-8; Male; Prospective Studies; Receptors, Tumor Necrosis Factor, Type II; Visual Acuity; Wet Macular Degeneration

To evaluate the dynamic changes of the aqueous humor levels of inflammatory factors between patients receiving intravitreal ranibizumab injection (IRI) and aflibercept injection (IAI) in patients with exudative age-related macular degeneration (AMD).. The study was performed on 30 eyes with AMD that were scheduled to receive 3 doses of IRI (15 eyes) or IAI (15 eyes) at monthly intervals. Aqueous humor samples were collected when injection was done. The concentrations of VEGF, monocyte chemoattractant protein 1 (MCP-1), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, and IL-8 were measured in aqueous humor samples from the 30 AMD patients and 10 cataract patients (as controls) by the suspension array method.. Aqueous levels of the inflammatory factors (MCP-1, PDGF-AA, IL-6, and IL-8) were significantly correlated with each other. In both the IRI-treated eyes and the IAI-treated eyes, visual acuity and central macular thickness improved significantly, and the aqueous level of VEGF showed a significant decrease. In IAI-treated eyes, the aqueous levels of MCP-1 and PDGF-AA were significantly decreased at 2 months.. These findings suggest that the inflammatory factors are involved in the pathogenesis of AMD and also the possibility that the interaction between these inflammatory factors and IRI or IAI is different.

Topics: Aged; Angiogenesis Inhibitors; Aqueous Humor; Chemokine CCL2; Cytokines; Female; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Interleukin-8; Intravitreal Injections; Macula Lutea; Male; Platelet-Derived Growth Factor; Prospective Studies; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration

Inflammation and immune-mediated processes are pivotal to the pathogenic progression of age-related macular degeneration (AMD). Although plasma levels of C-reactive protein (CRP) have been shown to be associated with an increased risk for AMD, the pathophysiological importance of the prototypical acute-phase reactant in the etiology of the disease is unknown, and data regarding the exact role of CRP in ocular inflammation are limited. In this study, we provide mechanistic insight into how CRP contributes to the development of AMD. In particular, we show that monomeric CRP (mCRP) but not the pentameric form (pCRP) upregulates IL-8 and CCL2 levels in retinal pigment epithelial cells. Further, we show that complement factor H (FH) binds mCRP to dampen its proinflammatory activity. FH from AMD patients carrying the "risk" His402 polymorphism displays impaired binding to mCRP, and therefore proinflammatory effects of mCRP remain unrestrained.

Topics: Aged; C-Reactive Protein; Cell Line; Chemotaxis, Leukocyte; Complement Factor H; Cytokines; Down-Regulation; Female; Genetic Predisposition to Disease; Humans; Inflammation; Interleukin-8; Leukocytes, Mononuclear; Male; Polymorphism, Genetic; Protein Binding; Protein Multimerization; Retinal Pigment Epithelium; Wet Macular Degeneration

To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking.. Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A→T, CFH rs1061170 T→C, ARMS2 rs10490924 G→T and C3 rs2230199 C→G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed.. Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD.. Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD.

Topics: Aged; Aged, 80 and over; Complement C3; Complement Factor H; Female; Genotype; Geographic Atrophy; Humans; Interleukin-8; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Retrospective Studies; Risk Factors; Smoking; Wet Macular Degeneration

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Bevacizumab; Coloring Agents; Complement Factor H; Female; Fluorescein Angiography; Genotype; Humans; Indocyanine Green; Interleukin-8; Male; Middle Aged; Polymorphism, Single Nucleotide; Prospective Studies; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration

To study the association of single-nucleotide polymorphisms of interleukin 8, vascular endothelial growth factor, erythropoietin, complement factor H, complement component C3, and LOC387715 genes with the response to bevacizumab treatment in exudative age-related macular degeneration.. Clinical records, smoking history, optical coherence tomography, and angiographies of 96 bevacizumab-treated exudative age-related macular degeneration patients were analyzed retrospectively. Blood DNA was collected. Based on the disappearance of intra- or subretinal fluid in optical coherence tomography, patients were graded as responders, partial responders, or nonresponders after 3 initial treatment visits and a median time of 3.5 months.. Interleukin 8 promoter polymorphism -251A/T was significantly associated with persisting fluid in optical coherence tomography. The A allele was more frequent in nonresponders than in responders (P = 0.033). In multivariate modeling, the AA genotype of -251A/T (P = 0.043) and occult (P = 0.042) or predominantly classic (P = 0.040) lesions predicted poorer outcome. Visual acuity change was better in responders than in nonresponders (P = 0.006). Baseline lesion size (P = 0.006) and retinal cysts after the treatment (P < 0.001) correlated with less visual acuity gain.. The A allele and the homozygous AA genotype of interleukin 8 -251A/T were associated with anatomical nonresponse to bevacizumab treatment.

Topics: Aged; Aged, 80 and over; Alleles; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Bevacizumab; Complement C3; Complement Factor H; Exudates and Transudates; Female; Genotype; Humans; Interleukin-8; Intravitreal Injections; Male; Middle Aged; Pharmacogenetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Prospective Studies; Proteins; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration