Development of a simplified human embryonic stem cell-based retinal pre-organoid model for toxicity evaluations of common pollutants.

IF 1.6 4区 医学 Q3 OPHTHALMOLOGY
Cutaneous and Ocular Toxicology Pub Date : 2023-12-01 Epub Date: 2023-08-27 DOI:10.1080/15569527.2023.2249988
Yue Wang, Nuoya Yin, Renjun Yang, Miaomiao Zhao, Shichang Li, Shuxian Zhang, Yanyi Zhao, Francesco Faiola
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引用次数: 0

Abstract

Objective: To explore the retinal toxicity of pharmaceuticals and personal care products (PPCPs), flame retardants, bisphenols, phthalates, and polycyclic aromatic hydrocarbons (PAHs) on human retinal progenitor cells (RPCs) and retinal pigment epithelial (RPE) cells, which are the primary cell types at the early stages of retinal development, vital for subsequent functional cell type differentiation, and closely related to retinal diseases.

Materials and methods: After 23 days of differentiation, human embryonic stem cell (hESC)-based retinal pre-organoids, containing RPCs and RPE cells, were exposed to 10, 100, and 1000 nM pesticides (butachlor, terbutryn, imidacloprid, deltamethrin, pendimethalin, and carbaryl), flame retardants (PFOS, TBBPA, DBDPE, and TDCIPP), PPCPs (climbazole and BHT), and other typical pollutants (phenanthrene, DCHP, and BPA) for seven days. Then, mRNA expression changes were monitored and compared.

Results: (1) The selected pollutants did not show strong effects at environmental and human-relevant concentrations, although the effects of flame retardants were more potent than those of other categories of chemicals. Surprisingly, some pollutants with distinct structures showed similar adverse effects. (2) Exposure to pollutants induced different degrees of cell detachment, probably due to alterations in extracellular matrix and/or cell adhesion.

Conclusions: In this study, we established a retinal pre-organoid model suitable for evaluating multiple pollutants' effects, and pointed out the potential retinal toxicity of flame retardants, among other pollutants. Nevertheless, the potential mechanisms of toxicity and the effects on cell detachment are still unclear and deserve further exploration. Additionally, this model holds promise for screening interventions aimed at mitigating the detrimental effects of these pollutants.

开发一种用于常见污染物毒性评估的简化的基于人类胚胎干细胞的视网膜类器官前模型。
目的:探讨药物和个人护理产品(PPCPs)、阻燃剂、双酚、邻苯二甲酸酯和多环芳烃(PAHs)对视网膜发育早期的主要细胞类型人类视网膜祖细胞(RPCs)和视网膜色素上皮(RPE)细胞的视网膜毒性,对随后的功能细胞类型分化至关重要,并且与视网膜疾病密切相关。材料和方法:23之后 在分化的几天内,将含有RPC和RPE细胞的基于人胚胎干细胞(hESC)的视网膜前类器官暴露于10、100和1000 nM杀虫剂(丁草胺、terbutryn、吡虫啉、溴氰菊酯、二甲基戊烯和西维因)、阻燃剂(PFOS、TBBPA、DBDPE和TDCIPP)、PPCPs(climbazole和BHT)和其他典型污染物(菲、DCHP和BPA),持续7天。然后,监测并比较mRNA表达的变化。结果:(1)选定的污染物在环境和人类相关浓度下没有表现出强烈的影响,尽管阻燃剂的影响比其他类别的化学品更大。令人惊讶的是,一些具有不同结构的污染物显示出类似的不良影响。(2) 暴露于污染物引起不同程度的细胞分离,可能是由于细胞外基质和/或细胞粘附的改变。结论:在本研究中,我们建立了一个适合评估多种污染物影响的视网膜前类器官模型,并指出了阻燃剂和其他污染物对视网膜的潜在毒性。然而,毒性的潜在机制和对细胞分离的影响仍不清楚,值得进一步探索。此外,该模型有望对旨在减轻这些污染物有害影响的干预措施进行筛选。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.30
自引率
6.20%
发文量
40
审稿时长
1 months
期刊介绍: Cutaneous and Ocular Toxicology is an international, peer-reviewed journal that covers all types of harm to cutaneous and ocular systems. Areas of particular interest include pharmaceutical and medical products; consumer, personal care, and household products; and issues in environmental and occupational exposures. In addition to original research papers, reviews and short communications are invited, as well as concise, relevant, and critical reviews of topics of contemporary significance.
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