Serum cytokines as biomarkers for age-related macular degeneration

Nassar, Khaled; Grisanti, Salvatore; Elfar, Elshaymaa; Lüke, Julia; Lüke, Matthias; Grisanti, Swaantje

doi:10.1007/s00417-014-2738-8

Cited by 100 publications

(96 citation statements)

References 20 publications

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“…Many studies in animal models have established causal links between retinal damage and proinflammatory pathways [20][21][22]. In humans, many studies have shown that AMD patients presented higher expression of proinflammatory cytokines and altered phenotype and functions of immune cells [16,23,24]. This study demonstrated that AMD patients also presented an imbalance in the composition of CD4 + T …”

Section: Discussionmentioning

confidence: 56%

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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: Discussionmentioning

confidence: 56%

“…Th17 cells also secrete TNF in addition to IL-17 and are implicated in multiple inflammatory mechanisms [15]. Interestingly, AMD patients presented increased serum levels of proinflammatory cytokines, including IL-1β, TNF, and IL-17 [16]. Therefore, in this study, we examined the Th1 and Th17 cells in AMD patients.…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Wang

2017

Cell Physiol Biochem

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“…Also, an association between two single nucleotide polymorphisms in the IL-17 gene, rs2275913G/A and rs3748067C/T and AMD was reported 42 . IL-17 and TNF-α have been observed at higher concentrations in AMD patients and may be linked to a more favorable response to anti-VEGF therapy 43 . Altered DNA methylation of the IL17RC promoter has been observed in AMD patients leading to an elevated expression of its protein and messenger RNA in peripheral blood and affected parts of the retina and choroid 44 .…”

Section: Discussionmentioning

confidence: 99%

Systemic frequencies of T helper 1 and T helper 17 cells in patients with age-related macular degeneration: A case-control study

Singh

Subhi

Nielsen

et al. 2017

Sci Rep

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Age-related macular degeneration (AMD) is a degenerative disease of the retina and a leading cause of irreversible vision loss. We investigated the systemic differences in the frequency of T helper (Th) 1 and Th17 cells in patients with non-exudative and exudative AMD and compared to age-matched controls. Flow cytometry was used to determine the systemic frequency of Th1 (CD4+CXCR3+IL12RB2+) and Th17 (CD4+CCR6+IL23R+) cells, and percentage of CD4+ T-cells expressing CXCR3, IL12RB2, CCR6, IL23R, and co-expressing CXCR3 and CCR6. The frequency of Th1 cells and CXCR3+ CD4+ T-cells was lower in patients with exudative AMD. A significant age-dependent decrement in Th1 was observed in controls, but not in non-exudative or exudative AMD. This may be related to the CXCR3+ CD4+ T-cells, which showed similar pattern in controls, but not in non-exudative or exudative AMD. No significant group differences were observed for the frequency of Th17 cells. Correlation networks found several differences between controls and AMD. These data suggests the involvement of the adaptive immune system in AMD and supports the notion of AMD as a systemic disease. Our observations warrant further investigation into the role of the adaptive immune system in the pathogenesis of AMD.

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“…Patients with AMD have increased plasma levels of inflammatory cytokines such as IL-1α, IL-1β, IL-4, IL-5, IL-13, and IL-17 [35]. The strongest links with disease are related to the pro-inflammatory cytokines IL-1, IL-6, and TNF-α, which are released from the choroid of patients with AMD and can immune-mediated retinal damage [17].…”

Section: Amd and Serological Biomarkersmentioning

confidence: 99%

Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

Adamus

2017

Autoimmunity Reviews

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Age-related macular degeneration (AMD) is a major cause of central vision loss in persons over 55 years of age in developed countries. AMD is a complex disease in which genetic, environmental and inflammatory factors influence its onset and progression. Elevation in serum anti-retinal autoantibodies, plasma and local activation of complement proteins of the alternative pathway, and increase in secretion of proinflammatory cytokines have been seen over the course of disease. Genetic studies of AMD patients confirmed that genetic variants affecting the alternative complement pathway have a major influence on AMD risk. Because the heterogeneity of this disease there is no sufficient strategy to identify the disease onset and progression sole based eye examination, thus identification of reliable serological biomarkers for diagnosis, prognosis and response to treatment by sampling patient's blood. This review provides an outline of the current knowledge on possible serological (autoantibodies, complement factors, cytokines, chemokines) and related genetic biomarkers relevant to the pathology of AMD, and discusses their application for prediction of disease activity and prognosis in AMD.

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Serum cytokines as biomarkers for age-related macular degeneration

Cited by 100 publications

References 20 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

Systemic frequencies of T helper 1 and T helper 17 cells in patients with age-related macular degeneration: A case-control study

Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

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