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利用诱导多能干细胞衍生的视网膜色素上皮细胞揭示眼部结核病中的宿主-病原体相互作用:一种反向转化模型。

Exploiting induced pluripotent stem cell-derived retinal pigment epithelium to unravel host-pathogen interaction in ocular tuberculosis: a reverse translational model.

作者信息

Putera Ikhwanuliman, van de Meerendonk Sanne, Nagtzaam Nicole M A, La Distia Nora Rina, Rombach Saskia M, de Steenwinkel Jurriaan E M, Vingerling Johannes R, Dik Willem A, van Hagen P Martin

机构信息

Department of Ophthalmology, Faculty of Medicine, University of Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, Netherlands.

出版信息

Front Ophthalmol (Lausanne). 2025 Jun 4;5:1610215. doi: 10.3389/fopht.2025.1610215. eCollection 2025.

DOI:10.3389/fopht.2025.1610215
PMID:40535229
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12173865/
Abstract

() can infect the retinal pigment epithelium (RPE) cells. Current research models for ocular tuberculosis (OTB) only rely on RPE cell culture approaches. Until now it remains unclear why only a minority of patients with active systemic tuberculosis (TB) develops concurrent OTB. There is significant variation in the clinical manifestations of OTB, which is potentially influenced by ethnic differences and diversity in mycobacterial strains. To better understand the immunopathobiology of OTB, particularly an individual's susceptibility to -infection and the specific host response, cell culture systems utilizing induced pluripotent stem cells (iPSC)-derived RPE cells offer a promising model to better mimic the disease. With this technology, RPE cells can be generated from specific patients of interest, enabling to test hypotheses in a bench to bedside or reverse manner. In this current study, we explore the utility of iPSC-derived RPE cells as an model for OTB. Such an approach would overcome drawbacks associated with the currently commonly used "general" RPE cell lines as disease model. The application of iPSC-derived RPE cells offers promising options for the identification of novel biomarkers and to study individualized drug screening methods for host-directed therapy of OTB, in order to restore and maintain vision in OTB patients with sight-threatening disease.

摘要

()可感染视网膜色素上皮(RPE)细胞。目前眼部结核病(OTB)的研究模型仅依赖于RPE细胞培养方法。到目前为止,仍不清楚为什么只有少数活动性系统性结核病(TB)患者会并发OTB。OTB的临床表现存在显著差异,这可能受种族差异和分枝杆菌菌株多样性的影响。为了更好地理解OTB的免疫病理生物学,特别是个体对感染的易感性和特定的宿主反应,利用诱导多能干细胞(iPSC)衍生的RPE细胞的细胞培养系统提供了一个有前景的模型,能更好地模拟该疾病。借助这项技术,可以从感兴趣的特定患者中生成RPE细胞,从而能够以从实验台到床边或反向的方式检验假设。在本研究中,我们探索了iPSC衍生的RPE细胞作为OTB模型的效用。这种方法将克服与目前常用的作为疾病模型的“通用”RPE细胞系相关的缺点。iPSC衍生的RPE细胞的应用为鉴定新型生物标志物以及研究针对OTB宿主导向治疗的个体化药物筛选方法提供了有前景的选择,以便恢复和维持患有威胁视力疾病的OTB患者的视力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/12173865/1fda04aabc23/fopht-05-1610215-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/12173865/b7d8bb1fca7e/fopht-05-1610215-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/12173865/1fda04aabc23/fopht-05-1610215-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/12173865/b7d8bb1fca7e/fopht-05-1610215-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/132f/12173865/1fda04aabc23/fopht-05-1610215-g002.jpg

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本文引用的文献

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iPSC-derived retinal pigment epithelium: an in vitro platform to reproduce key cellular phenotypes and pathophysiology of retinal degenerative diseases.诱导多能干细胞衍生的视网膜色素上皮细胞:用于重现视网膜退行性疾病关键细胞表型和病理生理学的体外平台。
Stem Cells Transl Med. 2025 Mar 18;14(3). doi: 10.1093/stcltm/szae097.
2
RNASeq profiling of retinal pigment epithelial cells derived from induced pluripotent stem cells revealed 3 genes involved in lipid homeostasis in age-related macular degeneration.诱导多能干细胞衍生的视网膜色素上皮细胞的 RNA 测序分析揭示了 3 个与年龄相关性黄斑变性中脂质动态平衡相关的基因。
Exp Eye Res. 2024 Sep;246:109999. doi: 10.1016/j.exer.2024.109999. Epub 2024 Jul 10.
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Clinical Features and Predictors of Treatment Outcome in Patients with Ocular Tuberculosis from the Netherlands and Indonesia: The OculaR TB in Low versus High Endemic Countries (ORTEC) Study.
荷兰和印度尼西亚眼结核患者的临床特征及治疗结果预测因素:低流行国家与高流行国家的眼结核(ORTEC)研究
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Relapse in ocular tuberculosis: relapse rate, risk factors and clinical management in a non-endemic country.眼结核复发:在非流行国家的复发率、危险因素和临床管理。
Br J Ophthalmol. 2024 Nov 22;108(12):1642-1651. doi: 10.1136/bjo-2024-325207.
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Induced Pluripotent Stem Cells in Drug Discovery and Neurodegenerative Disease Modelling.诱导多能干细胞在药物发现和神经退行性疾病建模中的应用。
Int J Mol Sci. 2024 Feb 18;25(4):2392. doi: 10.3390/ijms25042392.
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