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The role of the cytokine TNF-α in choroidal neovascularization: a systematic review

Eye volume 38, pages 25–32 (2024)Cite this article

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Abstract

TNF-α is a multifunctional cytokine produced by macrophages and T cells. This proinflammatory substance is considered to play a crucial role in the inflammatory process associated with age-related macular degeneration (AMD). The current review aimed to describe evidence for an association between TNF-α and AMD reported in various studies. The MEDLINE, Embase, PubMed and Global Health databases were systematically searched to identify studies that investigated the role of TNF-α in AMD. A total of 24 studies were deemed eligible for the review. To better understand and integrate the evidence, the studies were categorised into four major groups in relation to the role of TNF-α in AMD: (1) those examining biological signalling pathways through which TNF-α exerts its effect; (2) investigating levels of TNF-α; (3) exploring the genetics underlying the role of TNF-α; and (4) assessing anti-TNF-α agents as potential treatments for AMD. TNF-α is thought to directly contribute to choroidal neovascularization (CNV) enhancement and has been shown to exert its effect by augmenting the inflammatory response through other signalling pathways. Additionally, different genes have been found to be associated with activities linked to TNF-α in AMD. Overall, measurement of systemic and local levels of TNF-α has not yielded consistent findings, with variable conclusions for the role of anti-TNF-α agents in remission of AMD symptoms. The role of TNF-α in neovascular AMD is not clear, and not all anti-TNF-α agents are safe. The potential of this cytokine in atrophic AMD has not been examined. Future studies should address these unresolved questions.

摘要

TNF-α是由巨噬细胞和T细胞产生的多功能细胞因子。其在与年龄相关性黄斑变性 (AMD) 的炎症过程中起重要作用。本综述旨在描述各种研究中报告的TNF-α和AMD相关联的证据。对MEDLINE、Embase、PubMed和全球健康数据库进行搜索, 确定有关TNF-α在AMD中的作用的研究。共有24项研究符合本综述条件。为更好地理解和整合证据, 根据TNF-α在AMD中的作用, 将文献分为四大类: (1) TNF-α发挥作用的细胞信号通路; (2) TNF-α的水平; (3) 探索TNF-α潜在的遗传学作用; (4) 评估抗TNF-α药物作为AMD的潜在治疗。TNF-α可直接导致脉络膜新生血管 (CNV), 并且通过其他信号通路增强炎症反应发挥其作用。此外, 发现不同基因与TNF-α在AMD的相关病理作用有关。总之, 对于TNF-α全身和局部水平还无一致结果, 对于抗TNF-α药物在缓解AMD症状的作用方面得出了多种结论。TNF-α抗新生血管的作用还不清楚, 并非所有抗TNF-α药物都是安全的。这种细胞因子在萎缩性AMD中的潜力尚未得到研究。未来的研究应解决这些尚未解决的问题。

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  1. School of Medicine, European University Cyprus, Nicosia, Cyprus

    Zois Papadopoulos

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Appendix 1 Search terms and articles retrieved from databases

Appendix 1 Search terms and articles retrieved from databases

 

Database

Search terms

Results

1

Embase

1974 to 2022 week 17

1# exp retina macula age-related degeneration/or exp age-related macular degeneration/or exp

“neovascularization (pathology)”

68090

2# exp age-related macular degeneration/or age-related maculopathy

10376

3# exp macular degeneration

16175

4# tumour necrosis factor alpha.mp. or exp tumour necrosis factor

140867

5# (1 OR 2 OR 3)

74434

6# 4 AND 5

703

2

Ovid MEDLINE

1947 to 26 April 2022

1# exp retina macula age-related degeneration/or exp age-related macular degeneration/or exp “neovascularization (pathology)”

23839

2# exp age-related macular degeneration/or age-related maculopathy

23976

3# exp macular degeneration

23839

4# tumour necrosis factor alpha.mp. or exp tumour necrosis factor

129129

5# (1 OR 2 OR 3)

23976

6# 4 AND 5

95

2

Global Health 1973 to 2022 Week 17

1# exp retina macula age-related degeneration/or exp age-related macular degeneration/or exp “neovascularization (pathology)”

0

2# exp age-related macular degeneration/or age-related maculopathy

217

3# exp macular degeneration

2071

4# tumour necrosis factor alpha.mp. or exp tumour necrosis factor

6125

5# (1 OR 2 OR 3)

2074

6# 4 AND 5

0

2# “macular degeneration”[MeSH Terms] OR agerelated macular degeneration [Text Word])”

19467

3# “tumour necrosis factor-alpha”[MeSH Terms]

123441

5# (“Age-related macular degeneration MeSH major topics” “Macular Degeneration”[Majr]) AND “Tumour Necrosis Factor-alpha”[Mesh]

90

2

PubMed

1973 to 2022 Week 17

1# Age-related macular degeneration MeSH major topics

32609

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Papadopoulos, Z. The role of the cytokine TNF-α in choroidal neovascularization: a systematic review. Eye 38, 25–32 (2024). https://doi.org/10.1038/s41433-023-02634-5

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