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外部电场调节神经元发育并增加视网膜类器官中的光感受器数量。

Extrinsic electric field modulates neuronal development and increases photoreceptor population in retinal organoids.

作者信息

Rajendran Nair Deepthi S, Gupta Anika, Iseri Ege, Wei Tianyuan, Phuong Quach Le Tam, Seiler Magdalene J, Lazzi Gianluca, Thomas Biju B

机构信息

Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA, United States.

Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, United States.

出版信息

Front Neurosci. 2024 Nov 29;18:1438903. doi: 10.3389/fnins.2024.1438903. eCollection 2024.

DOI:10.3389/fnins.2024.1438903
PMID:39678532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11639233/
Abstract

INTRODUCTION

Considering the significant role played by both intrinsic and extrinsic electric fields in the growth and maturation of the central nervous system, the impact of short exposure to external electric fields on the development and differentiation of retinal organoids was investigated.

METHODS

Retinal organoids derived from human embryonic stem cells were used at day 80, a key stage in their differentiation. A single 60-minute exposure to a biphasic electrical field was administered to assess its influence on retinal cell populations and maturation markers. Immunohistochemistry, qPCR, and RNA sequencing were employed to evaluate cell type development and gene expression changes.

RESULTS

Electrical stimulation significantly enhanced neuronal development and increased the population of photoreceptors within the organoids. RNA sequencing data showed upregulated expression of genes related to rod photoreceptors, Müller cells, horizontal cells, and amacrine cells, while genes associated with retinal pigment epithelium and retinal ganglion cells were downregulated. Variations in development and maturation were observed depending on the specific parameters of the applied electric field.

DISCUSSION

These findings highlight the significant impact of extrinsic electrical fields on early retinal development and suggest that optimizing electrical field parameters could effectively address certain limitations in retinal organoid technology, potentially reducing the reliance on chemicals and small molecules.

摘要

引言

鉴于内在和外在电场在中枢神经系统生长和成熟过程中发挥的重要作用,研究了短期暴露于外部电场对视网膜类器官发育和分化的影响。

方法

在人胚胎干细胞来源的视网膜类器官分化的关键阶段第80天使用这些类器官。施加单次60分钟的双相电场以评估其对视网膜细胞群体和成熟标志物的影响。采用免疫组织化学、定量聚合酶链反应(qPCR)和RNA测序来评估细胞类型发育和基因表达变化。

结果

电刺激显著促进了神经元发育,并增加了类器官内光感受器的数量。RNA测序数据显示,与视杆光感受器、穆勒细胞、水平细胞和无长突细胞相关的基因表达上调,而与视网膜色素上皮和视网膜神经节细胞相关的基因表达下调。根据所施加电场的具体参数观察到发育和成熟的差异。

讨论

这些发现突出了外在电场对早期视网膜发育的重大影响,并表明优化电场参数可以有效解决视网膜类器官技术中的某些局限性,有可能减少对化学物质和小分子的依赖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/aff163ade18d/fnins-18-1438903-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/3ece984659a8/fnins-18-1438903-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/629e901d0331/fnins-18-1438903-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/37a79fa5c0a2/fnins-18-1438903-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/81a285bf6507/fnins-18-1438903-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/aff163ade18d/fnins-18-1438903-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/3ece984659a8/fnins-18-1438903-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/629e901d0331/fnins-18-1438903-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/37a79fa5c0a2/fnins-18-1438903-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/81a285bf6507/fnins-18-1438903-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2207/11639233/aff163ade18d/fnins-18-1438903-g005.jpg

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本文引用的文献

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Retinal Pigment Epithelium Cell Development: Extrapolating Basic Biology to Stem Cell Research.
视网膜色素上皮细胞发育:将基础生物学外推至干细胞研究
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