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DOI10.1073/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
ISSN0027-8424
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
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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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