Genetics of Immunological and Inflammatory Components in Age-related Macular Degeneration

Tuo, Jingsheng; Grob, Seanna; Zhang, Kang; Chan, Chi‐Chao

doi:10.3109/09273948.2011.628432

Cited by 75 publications

(60 citation statements)

References 114 publications

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“…Many cells of the innate and adaptive immune system, including mast cells, macrophages, and lymphocytes, have been found in macular lesions and the adjacent choroid area [7,8]. Furthermore, genetic polymorphisms in many immune-related genes have been associated with altered AMD risk [9]. Together, these results suggest that dysregulation in the immune system may contribute to AMD progression, but the mechanistic details remain to be established.…”

Section: Introductionmentioning

confidence: 86%

Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration

Chen

Wang

2017

Cell Physiol Biochem

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Background/Aims: Age-related macular degeneration (AMD) is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. Methods: We examined the CD4 + T cell compartments and their functions in AMD patients. Results: AMD patients presented significantly higher frequencies of interferon (IFN)-γ-expressing and interleukin (IL)-17-expressing CD4 + T cells than healthy controls. The levels of IFN-γ and IL-17 expression by CD4 + T cells were significantly higher in AMD patients. These IFN-γ-expressing Th1 cells and IL-17-expressing Th17 cells could be selectively enriched by surface CCR3 + and CCR4 + CCR6 + expression, respectively. Th1 and Th17 cells from AMD patients promoted the differentiation of monocytes toward M1 macrophages, which were previously associated with retinal damage. Th1 and Th17 cells also increased the level of MHC class I expression in human retinal pigment epithelial (RPE)-1 cells, while Th1 cells increased the frequency of MHC class II-expressing RPE-1 cells. These proinflammatory effects were partly, but not entirely, induced by the secretion of IFN-γ and IL-17. Conclusions: This study demonstrated an enrichment of Th1 cells and Th17 cells in AMD patients. These Th1 and Th17 cells possessed proinflammatory roles in an IFN-γ-and IL-17-dependent fashion, and could potentially serve as therapeutic targets.

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Section: Introductionmentioning

confidence: 86%

Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration

Chen

Wang

2017

Cell Physiol Biochem

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“…Choroidal neovascularization (CNV), the hallmark of wet AMD, was shown to be dependent on inflammatory cytokines, as well as inflammatory signals. Genetic studies also demonstrated strong associations between AMD and several gene variants in genes coding for inflammatory mediators and complement proteins (1)(2)(3).…”

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confidence: 99%

IL-23–Independent Induction of IL-17 from γδT Cells and Innate Lymphoid Cells Promotes Experimental Intraocular Neovascularization

Hasegawa

Sonoda

Shichita

et al. 2013

The Journal of Immunology

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Choroidal neovascularization (CNV) is a characteristic of age-related macular degeneration. Genome-wide association studies have provided evidence that the immune system is involved in the pathogenesis of age-related macular degeneration; however, the role of inflammatory cytokines in CNV has not been established. In this study, we demonstrated that IL-17 had a strong potential for promoting neovascularization in a vascular endothelial growth factor–independent manner in laser-induced experimental CNV in mice. Infiltrated γδT cells and Thy-1+ innate lymphoid cells, but not Th17 cells, were the main sources of IL-17 in injured eyes. IL-23 was dispensable for IL-17 induction in the eye. Instead, we found that IL-1β and high-mobility group box 1 strongly promoted IL-17 expression by γδT cells. Suppression of IL-1β and high-mobility group box 1, as well as depletion of γδT cells, reduced IL-17 levels and ameliorated experimental CNV. Our findings suggest the existence of a novel inflammatory cytokine network that promotes neovascularization in the eye.

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“…Genome-wide linkage analyses and candidate gene-based association studies have suggested and identified several chromosomal regions that may appear to contribute to AMD susceptibility [37,38,39]. To date, both 1q15–32 and 10q26 loci are the most strongly associated with disease [40]. Several independent studies have reported that a Y402H polymorphism in the CFH gene makes a substantial contribution to disease susceptibility with OR for AMD ranging between 2.4 and 4.6 for carriers of the H allele and between 3.3 and 7.4 for HH homozygotes [18,41,42].…”

Section: Discussionmentioning

confidence: 99%

Y402H Polymorphism in Complement Factor H and Age-Related Macular Degeneration in the Tunisian Population

Habibi¹,

Sfar²,

Kort

et al. 2013

Ophthalmic Res

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To evaluate a possible association between the complement factor H (CFH) Y402H polymorphism and susceptibility to age-related macular degeneration (AMD) in the Tunisian population, as well as the impact of the genotype distribution among different phenotypes and the response to treatment with intravitreal bevacizumab, exon 9 of CFH was analyzed for the Y402H polymorphism by direct sequencing in 135 healthy controls and 127 sporadic unrelated AMD patients classified into the following groups: 12 atrophic AMD (group G1), 115 exudative AMD (G2) and 10 AMD patients who had fibrovascular scarring (G3) that did not allow a precise grading of the phenotype. Seventy patients in G2 were treated with 1.25 mg intravitreal bevacizumab at 6-week intervals until choroidal neovascularization (CNV) was no longer active. The frequency of the CFH 402H allele was significantly higher in AMD patients than in controls (p = 2.62 × 10^–16). However, subgroup analysis does not reveal any association between the variant allele H and phenotypes of AMD or CNV. Also, there was no significant difference in response to bevacizumab treatment according to Y402H CFH genotype (p = 0.59). A strong association of the 402H allele with susceptibility to AMD in the Tunisian population was confirmed; however, this variant does not appear to be involved in the clinical progression of this disease or in the postintravitreal bevacizumab response.

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Genetics of Immunological and Inflammatory Components in Age-related Macular Degeneration

Cited by 75 publications

References 114 publications

Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration

Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration

IL-23–Independent Induction of IL-17 from γδT Cells and Innate Lymphoid Cells Promotes Experimental Intraocular Neovascularization

Y402H Polymorphism in Complement Factor H and Age-Related Macular Degeneration in the Tunisian Population

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