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DOI | 10.1073/pnas.2017198118 |
The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration | |
Leach L.L.; Hanovice N.J.; George S.M.; Gabriel A.E.; Gross J.M. | |
发表日期 | 2021 |
ISSN | 0027-8424 |
卷号 | 118期号:21 |
英文摘要 | Loss of the retinal pigment epithelium (RPE) because of dysfunction or disease can lead to blindness in humans. Harnessing the intrinsic ability of the RPE to self-repair is an attractive therapeutic strategy; however, mammalian RPE is limited in its regenerative capacity. Zebrafish possess tremendous intrinsic regenerative potential in ocular tissues, including the RPE, but little is known about the mechanisms driving RPE regeneration. Here, utilizing transgenic and mutant zebrafish lines, pharmacological manipulations, transcriptomics, and imaging analyses, we identified elements of the immune response as critical mediators of intrinsic RPE regeneration. After genetic ablation, the RPE express immune-related genes, including leukocyte recruitment factors such as interleukin 34. We demonstrate that macrophage/microglia cells are responsive to RPE damage and that their function is required for the timely progression of the regenerative response. These data identify the molecular and cellular underpinnings of RPE regeneration and hold significant potential for translational approaches aimed toward promoting a pro-regenerative environment in mammalian RPE. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | inflammation; macrophage; microglia; regeneration; Retinal pigment epithelium |
语种 | 英语 |
scopus关键词 | interleukin 34; adult; animal cell; animal experiment; animal tissue; apoptosis; Article; cell function; cell proliferation; controlled study; embryo; gene expression; immune response; macrophage; microglia; mutant; nonhuman; retinal pigment epithelium; tissue injury; tissue regeneration; transcriptomics; transgenic zebrafish; TUNEL assay; upregulation; vitreoretinopathy |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/238915 |
作者单位 | Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States; Department of Developmental Biology, University, Pittsburgh School of Medicine, Pittsburgh, PA 15213, United States |
推荐引用方式 GB/T 7714 | Leach L.L.,Hanovice N.J.,George S.M.,et al. The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration[J],2021,118(21). |
APA | Leach L.L.,Hanovice N.J.,George S.M.,Gabriel A.E.,&Gross J.M..(2021).The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration.Proceedings of the National Academy of Sciences of the United States of America,118(21). |
MLA | Leach L.L.,et al."The immune response is a critical regulator of zebrafish retinal pigment epithelium regeneration".Proceedings of the National Academy of Sciences of the United States of America 118.21(2021). |
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