EphB1 通过视网膜和视网膜 Müller 细胞的炎症途径导致视网膜损伤。

IF 1.8 3区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Vision Pub Date : 2024-03-22 eCollection Date: 2024-01-01
Li Liu, Youde Jiang, Mohamed Al-Shabrawey, Xiaobai Ren, Sui Wang, Jena J Steinle
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引用次数: 0

摘要

目的:研究Ephrin-B型受体1(EphB1)的增加是否会导致视网膜Müller细胞中的炎症介质:方法:检测糖尿病人和小鼠视网膜样本的 EphB1 蛋白水平。培养大鼠Müller细胞(rMC-1),并用EphB1 siRNA或ephrin B1-Fc处理,以探究在高糖条件下生长的细胞中的炎症介质。使用EphB1过表达腺相关病毒(AAV)增加体内Müller细胞中的EphB1。用EphB1过表达AAV处理的小鼠进行缺血再灌注(I/R),以探索EphB1对体内视网膜神经元变化的作用:结果:在糖尿病人和小鼠视网膜样本中,EphB1蛋白水平升高。敲除 EphB1 可降低在高糖条件下生长的 Müller 细胞中的炎症介质水平。Ephrin B1-Fc 增加了在正常和高葡萄糖条件下生长的 rMC-1 细胞中的炎症蛋白。对小鼠进行 I/R 处理会导致视网膜变薄和神经节细胞层细胞数量减少。在暴露于I/R并接受EphB1过表达AAV处理的小鼠中,这种情况加剧:结论:EphB1 在糖尿病人和小鼠的视网膜以及高糖处理的 Müller 细胞中增加。这种增加会导致炎症蛋白的产生。EphB1 还会增强视网膜对 I/R 的损伤。综上所述,抑制 EphB1 可为糖尿病视网膜病变提供一种新的治疗方案。
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EphB1 causes retinal damage through inflammatory pathways in the retina and retinal Müller cells.

Purpose: To examine whether increased ephrin type-B receptor 1 (EphB1) leads to inflammatory mediators in retinal Müller cells.

Methods: Diabetic human and mouse retinal samples were examined for EphB1 protein levels. Rat Müller cells (rMC-1) were grown in culture and treated with EphB1 siRNA or ephrin B1-Fc to explore inflammatory mediators in cells grown in high glucose. An EphB1 overexpression adeno-associated virus (AAV) was used to increase EphB1 in Müller cells in vivo. Ischemia/reperfusion (I/R) was performed on mice treated with the EphB1 overexpression AAV to explore the actions of EphB1 on retinal neuronal changes in vivo.

Results: EphB1 protein levels were increased in diabetic human and mouse retinal samples. Knockdown of EphB1 reduced inflammatory mediator levels in Müller cells grown in high glucose. Ephrin B1-Fc increased inflammatory proteins in rMC-1 cells grown in normal and high glucose. Treatment of mice with I/R caused retinal thinning and loss of cell numbers in the ganglion cell layer. This was increased in mice exposed to I/R and treated with the EphB1 overexpressing AAVs.

Conclusions: EphB1 is increased in the retinas of diabetic humans and mice and in high glucose-treated Müller cells. This increase leads to inflammatory proteins. EphB1 also enhanced retinal damage in response to I/R. Taken together, inhibition of EphB1 may offer a new therapeutic option for diabetic retinopathy.

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来源期刊
Molecular Vision
Molecular Vision 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
25
审稿时长
1 months
期刊介绍: Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.
期刊最新文献
Retraction: Swati Arora, Nagendra Verma. Exosomal microRNAs as potential biomarkers and therapeutic targets in corneal diseases. Molecular Vision 2024; 30:92-106. EphB1 causes retinal damage through inflammatory pathways in the retina and retinal Müller cells. Uveal melanoma cell lines Mel270 and 92.1 exhibit a mesenchymal phenotype and sensitivity to the cytostatic effects of transforming growth factor beta in vitro. Precise longitudinal monitoring of corneal change through in vivo confocal microscopy in a rat dry eye disease model. The generation and characterization of a transgenic zebrafish line with lens-specific Cre expression.
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