Interleukin Gene Polymorphisms in Age-Related Macular Degeneration

Tsai, Yi Yu; Lin, Jinyao; Wan, Lei; Lin, Hui Ju; Lee, Cheng Chun; Tsai, Chang Hai; Tsai, Fuu Jen; Tseng, Sung Huei

doi:10.1167/iovs.07-0125

Cited by 62 publications

(48 citation statements)

References 41 publications

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“…Puthothu et al (2006) reported that IL-8 polymorphism 781C/T is associated with the increased risk for asthma ( p = 0.011); at the same time, it is also associated with the increased risk for asthmatic population with the respiratory syncytial virus ( p = 0.034). In addition, the IL 8 781 T allele may also associated with increased risk of developing wet age-related macular degeneration (OR = 2.16, 95% CI, 1.58-2.94) (Tsai et al, 2008). The data mentioned previously clearly indicated that IL-8 polymorphism was associated with the inflammatory status as well as the risk of carcinoma.…”

Section: Discussionmentioning

confidence: 87%

The IL-8 Gene Polymorphisms and the Risk of the Hepatitis B Virus/Infected Patients

Qin

Deng²,

Liao³

et al. 2012

DNA and Cell Biology

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Interleukin-8 (IL-8) belongs to the superfamily of CXC chemokines, contributing to human cancer progression through potential mitogenic, angiogenic, and motogenic functions. We hypothesize that the functional polymorphism of IL-8 may influence the inflammatory process during pathological stage from hepatitis to hepatocellular carcinoma (HCC). Two polymorphisms in the IL-8 gene (-251A/T and +781C/T) were examined in 160 cases of chronic hepatitis B, 80 cases of hepatitis B virus (HBV)-related liver cirrhosis (LC), 150 cases of HBV-related HCC, and 150 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. In the LC group, the AA genotypes were associated with a significantly decreased risk of LC compared with the TT genotype (OR=0.14, 95% CI 0.02-0.87, p=0.035). The data also revealed that subjects with the A allele appeared to have lower susceptibility to LC than those with the T allele (OR=0.48, 95% CI 0.25-0.92, p=0.027). The +781C/T polymorphism of IL-8 was not found relevant to the liver diseases. This study indicated that the IL-8 gene -251 AA genotype might be a protect factor for LC.

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Section: Discussionmentioning

confidence: 87%

The IL-8 Gene Polymorphisms and the Risk of the Hepatitis B Virus/Infected Patients

Qin

Deng²,

Liao³

et al. 2012

DNA and Cell Biology

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“…Genetic polymorphisms in several cytokine genes have been described and demonstrated to influence gene transcription 108. Consistent with the role of inflammation in AMD, studies identified a strong association between a common variant (Y402H) of the gene for CFH and the risk of AMD 109–111.…”

Section: Cytokine Gene Polymorphisms In Neovascular Amdmentioning

confidence: 84%

“…A study found that only the presence of the IL-8+781T allele was significantly associated with wet-AMD, disagreeing with another study that only found association for the –251A allele 108 113. Hull et al showed that the functional allele of IL-8 may lie on chromosomes of the −251A/+781T haplotype, and −251A may not be functional 114.…”

Section: Cytokine Gene Polymorphisms In Neovascular Amdmentioning

confidence: 94%

Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy

Dias¹,

Rodrigues

Maia

et al. 2011

British Journal of Ophthalmology

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The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

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“…Several cytokine genes have been demonstrated to be associated with AMD including Il6, Il8, and IL10 (Tsai et al, 2008). Microarray data demonstrated that several genes are up-regulated in Il10 signaling in aged RPE/choroid from mouse (Chen et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Nanoceria inhibit expression of genes associated with inflammation and angiogenesis in the retina of Vldlr null mice

Kyosseva

Chen

Seal

et al. 2013

Experimental Eye Research

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Oxidative stress and inflammation are important pathological mechanisms in many neurodegenerative diseases, including age-related macular degeneration (AMD). The Very Low-Density Lipoprotein Receptor knockout mouse (Vldlr−/−) has been identified as a model for AMD and in particular for Retinal Angiomatous Proliferation (RAP). In this study we examined the effect of cerium oxide nanoparticles (nanoceria) that have been shown to have catalytic antioxidant activity, on expression of 88 major cytokines in the retinas of Vldlr−/− mice using a PCR array. A single intravitrial injection of nanoceria at P28 caused inhibition of pro-inflammatory cytokines and pro-angiogenic growth factors including Tslp, Lif, Il-3, Il-7, Vegfa, Fgf1, Fgf2, Fgf7, Egf, Efna 3, Lep, and up-regulation of several cytokines and anti-angiogenic genes in the Vldlr−/−retina within one week. We used the Ingenuity Pathway Analysis software to search for biological functions, pathways, and interrelationships between gene networks. Many of the genes whose activities were affected are involved in cell signaling, cellular development, growth and proliferation, and tissue development. Western blot analysis revealed that nanoceria inhibit the activation of ERK 1/2, JNK, p38 MAP kinase, and Akt. These data suggest that nanoceria may represent a novel therapeutic strategy to treat AMD, RAP, and other neurodegenerative diseases.

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Interleukin Gene Polymorphisms in Age-Related Macular Degeneration

Abstract: The data suggest that Taiwan Chinese carriers of the IL-8 +781 T allele, independent of the CFH Y402H polymorphism, are at increased risk of developing wet AMD.

Cited by 62 publications

References 41 publications

The IL-8 Gene Polymorphisms and the Risk of the Hepatitis B Virus/Infected Patients

The IL-8 Gene Polymorphisms and the Risk of the Hepatitis B Virus/Infected Patients

Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy

Nanoceria inhibit expression of genes associated with inflammation and angiogenesis in the retina of Vldlr null mice

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