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雷珠单抗改变渗出性年龄相关性黄斑变性患者外周血单个核细胞中金属蛋白酶及其组织抑制剂的表达。

Ranibizumab Modifies the Expression of Metalloproteinases and Their Tissue Inhibitors in Peripheral Blood Mononuclear Cells in Patients with Exudative Age-Related Macular Degeneration.

作者信息

Strzalka-Mrozik Barbara, Paprzycka Olga, Gruszka Oliwia, Madej Marcel, Kruszniewska-Rajs Celina, Gola Joanna Magdalena, Turek Artur

机构信息

Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland.

Silesia LabMed, Centre for Research and Implementation, Medical University of Silesia, 40-752 Katowice, Poland.

出版信息

J Clin Med. 2024 Jan 4;13(1):295. doi: 10.3390/jcm13010295.

DOI:10.3390/jcm13010295
PMID:38202302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10780024/
Abstract

BACKGROUND

Age-related macular degeneration (AMD) is the leading cause of vision loss in people over 60 years of age. Despite research, the causes of AMD remain unclear. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are known to be involved in AMD development, and anti-vascular endothelial growth factor therapy has revolutionized its treatment. This study aims to analyze the changes in gene expression in MMPs and TIMPS in patients with neovascular AMD before and after three doses of ranibizumab.

METHODS

The study involved 29 patients with neovascular AMD treated with ranibizumab. Peripheral blood mononuclear cells were collected before treatment and 24 h after the third dose of ranibizumab. We assessed MMP and TIMP gene expression profiles through oligonucleotide microarrays and validated selected differential genes using RT-qPCR.

RESULTS

A statistically significant change in the expression of six MMP- and TIMP-related genes was observed using oligonucleotide microarray. The mRNA levels of the two genes with the most significant fold changes, and , were then quantified using RT-qPCR. The results confirmed a statistically significant increase in expression and a decrease in levels, although this change was not statistically significant in the group before and after the third dose of ranibizumab.

CONCLUSION

Ranibizumab affects the systemic expression of MMP and TIMP-related genes in patients with neovascular AMD. Results from our exploratory study suggest that , in particular, may play a role in the treatment response, but further research is necessary.

摘要

背景

年龄相关性黄斑变性(AMD)是60岁以上人群视力丧失的主要原因。尽管进行了研究,但AMD的病因仍不清楚。已知基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)参与AMD的发展,并且抗血管内皮生长因子疗法彻底改变了其治疗方式。本研究旨在分析新血管性AMD患者在接受三剂雷珠单抗治疗前后MMPs和TIMPs基因表达的变化。

方法

该研究纳入了29例接受雷珠单抗治疗的新血管性AMD患者。在治疗前和第三剂雷珠单抗给药后24小时收集外周血单核细胞。我们通过寡核苷酸微阵列评估MMP和TIMP基因表达谱,并使用RT-qPCR验证选定的差异基因。

结果

使用寡核苷酸微阵列观察到六个与MMP和TIMP相关的基因表达有统计学意义的变化。然后使用RT-qPCR对两个折叠变化最显著的基因的mRNA水平进行定量。结果证实 表达有统计学意义的增加, 水平下降,尽管在第三剂雷珠单抗给药前后的组中这种变化没有统计学意义。

结论

雷珠单抗影响新血管性AMD患者中MMP和TIMP相关基因的全身表达。我们的探索性研究结果表明,特别是 可能在治疗反应中起作用,但需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de74/10780024/82e15e65eadc/jcm-13-00295-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de74/10780024/f182bca18a64/jcm-13-00295-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de74/10780024/7bc1de11e139/jcm-13-00295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de74/10780024/82e15e65eadc/jcm-13-00295-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de74/10780024/f182bca18a64/jcm-13-00295-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de74/10780024/7bc1de11e139/jcm-13-00295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de74/10780024/82e15e65eadc/jcm-13-00295-g003.jpg

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