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一种通过调节 NRF2 信号通路来防止视网膜瘢痕形成的生物功能聚合物。

A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway.

机构信息

Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

出版信息

Nat Commun. 2022 May 19;13(1):2796. doi: 10.1038/s41467-022-30474-6.

DOI:10.1038/s41467-022-30474-6
PMID:35589753
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9119969/
Abstract

One common cause of vision loss after retinal detachment surgery is the formation of proliferative and contractile fibrocellular membranes. This aberrant wound healing process is mediated by epithelial-mesenchymal transition (EMT) and hyper-proliferation of retinal pigment epithelial (RPE) cells. Current treatment relies primarily on surgical removal of these membranes. Here, we demonstrate that a bio-functional polymer by itself is able to prevent retinal scarring in an experimental rabbit model of proliferative vitreoretinopathy. This is mediated primarily via clathrin-dependent internalisation of polymeric micelles, downstream suppression of canonical EMT transcription factors, reduction of RPE cell hyper-proliferation and migration. Nuclear factor erythroid 2-related factor 2 signalling pathway was identified in a genome-wide transcriptomic profiling as a key sensor and effector. This study highlights the potential of using synthetic bio-functional polymer to modulate RPE cellular behaviour and offers a potential therapy for retinal scarring prevention.

摘要

视网膜脱离手术后视力丧失的一个常见原因是增生性和收缩性纤维细胞膜的形成。这种异常的伤口愈合过程是由上皮-间充质转化 (EMT) 和视网膜色素上皮 (RPE) 细胞的过度增殖介导的。目前的治疗主要依赖于手术切除这些膜。在这里，我们证明了一种生物功能聚合物本身能够预防增生性玻璃体视网膜病变实验兔模型中的视网膜瘢痕形成。这主要是通过网格蛋白依赖性聚合物胶束内化、下游对经典 EMT 转录因子的抑制、减少 RPE 细胞的过度增殖和迁移来介导的。核因子红细胞 2 相关因子 2 信号通路在全基因组转录组分析中被确定为关键的传感器和效应器。这项研究强调了使用合成生物功能聚合物来调节 RPE 细胞行为的潜力，并为预防视网膜瘢痕提供了一种潜在的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/24f5195a3569/41467_2022_30474_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/32329afc0296/41467_2022_30474_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/740b5127c0f5/41467_2022_30474_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/6836de2efeda/41467_2022_30474_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/71a13705a95f/41467_2022_30474_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/92087124230a/41467_2022_30474_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/24f5195a3569/41467_2022_30474_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/32329afc0296/41467_2022_30474_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/740b5127c0f5/41467_2022_30474_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/6836de2efeda/41467_2022_30474_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/71a13705a95f/41467_2022_30474_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/92087124230a/41467_2022_30474_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/020a/9119969/24f5195a3569/41467_2022_30474_Fig6_HTML.jpg

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[5]
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[6]
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[7]
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[8]
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[10]
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本文引用的文献

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