Human lens epithelial cells induce the inflammatory response when placed into the lens capsular bag model of posterior capsular opacification.

IF 1.4 3区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Vision Pub Date : 2024-10-08 eCollection Date: 2024-01-01
Samuel G Novo, Adam P Faranda, Justin C D'Antin, Yan Wang, Mahbubul Shihan, Rafael I Barraquer, Ralph Michael, Melinda K Duncan
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Abstract

Purpose: Cataracts are typically treated by phacoemulsification followed by intraocular lens implantation. Studies of mouse models of cataract surgery have revealed that lens epithelial cells rapidly remodel their transcriptome to express proinflammatory cytokines after lens fiber cell removal, but it is currently unknown whether this response is conserved in human lenses. This study seeks to fill this knowledge gap.

Methods: Human cadaver eyes from 70 to 89 year old individuals were prepared for the human capsular bag model of cataract surgery. The central epithelium was preserved in RNAlater during culture preparation, then the equatorial epithelium was either immediately preserved in RNAlater after the culture was created, or 24 h later. Gene expression profiles were generated by bulk sequencing of RNA isolated from these tissue samples. The transcriptomic response of human cadaver-derived lens epithelial cells to culture in this "capsular bag" model was characterized by bioinformatic analysis. The human response was directly compared to that of 24-month-old mouse lens epithelial cells subjected to fiber cell removal surgery.

Results: Human lens epithelial cells remodel approximately a third of their transcriptome by 24 h after surgery, and like mice, this response consists of induction of proinflammatory cytokine genes, upregulation of fibrotic markers and downregulation of genes controlling the lens epithelial phenotype.

Conclusions: These observations demonstrate that humans and mice have similar responses to cataract surgery and support the use of mice to study the response of lens epithelial cells to cataract surgery, suggesting that identified injury response mechanisms can be leveraged to elucidate new approaches to improve the outcomes of cataract surgery.

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将人晶状体上皮细胞置入后囊膜混浊的晶状体囊袋模型,诱导炎症反应。
目的:白内障的治疗通常采用超声乳化术后人工晶状体植入术。白内障手术小鼠模型的研究表明,晶状体上皮细胞在晶状体纤维细胞去除后迅速重塑其转录组以表达促炎细胞因子,但目前尚不清楚这种反应是否在人类晶状体中保守。本研究试图填补这一知识空白。方法:制备70 ~ 89岁人尸体眼,用于白内障手术的人囊袋模型。在培养准备过程中,将中央上皮保存在RNAlater中,然后在培养完成后立即或24 h后将赤道上皮保存在RNAlater中。基因表达谱是通过从这些组织样本中分离的RNA的批量测序产生的。生物信息学分析了人尸体来源的晶状体上皮细胞对这种“荚膜袋”模型的转录组反应。人类的反应直接与24个月大的小鼠晶状体上皮细胞进行纤维细胞去除手术的反应进行比较。结果:人类晶状体上皮细胞在手术后24小时内重塑了大约三分之一的转录组,与小鼠一样,这种反应包括诱导促炎细胞因子基因、上调纤维化标志物和下调控制晶状体上皮表型的基因。结论:这些观察结果表明,人类和小鼠对白内障手术有相似的反应,并支持使用小鼠研究晶状体上皮细胞对白内障手术的反应,表明已确定的损伤反应机制可以用来阐明改善白内障手术结果的新方法。
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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.
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