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Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy
The corneal endothelium is critical for maintaining corneal clarity by mediating hydration through barrier and pump functions. Progressive loss of corneal endothelial cells during aging has been associated with the development of Fuchs endothelial corneal dystrophy (FECD), one of the main causes of...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807987/ https://www.ncbi.nlm.nih.gov/pubmed/35141048 http://dx.doi.org/10.1016/j.omtn.2022.01.005 |
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author | Wang, Qun Dou, Shengqian Zhang, Bin Jiang, Hui Qi, Xia Duan, Haoyun Wang, Xin Dong, Chunxiao Zhang, Bi Ning Xie, Lixin Cao, Yihai Zhou, Qingjun Shi, Weiyun |
author_facet | Wang, Qun Dou, Shengqian Zhang, Bin Jiang, Hui Qi, Xia Duan, Haoyun Wang, Xin Dong, Chunxiao Zhang, Bi Ning Xie, Lixin Cao, Yihai Zhou, Qingjun Shi, Weiyun |
author_sort | Wang, Qun |
collection | PubMed |
description | The corneal endothelium is critical for maintaining corneal clarity by mediating hydration through barrier and pump functions. Progressive loss of corneal endothelial cells during aging has been associated with the development of Fuchs endothelial corneal dystrophy (FECD), one of the main causes of cornea-related vision loss. The mechanisms underlying FECD development remain elusive. Single-cell RNA sequencing of isolated healthy human corneas discovered 4 subpopulations of corneal endothelial cells with distinctive signatures. Unsupervised clustering analysis uncovered nuclear enriched abundant transcript 1 (NEAT1), a long non-coding RNA (lncRNA), as the top expressed gene in the C0-endothelial subpopulation, but markedly downregulated in FECD. Consistent with human corneas, a UVA-induced mouse FECD model validated the loss of NEAT1 expression. Loss of NEAT1 function by an in vivo genetic approach reproduced the exacerbated phenotype of FECD by ablating corneal endothelial cells. Conversely, gain of function by a CRISPR-activated adenoviral delivery system protected corneas from UVA-induced FECD. Our findings provide novel mechanistic insights into the development of FECD, and targeting NEAT1 offers an attractive approach for treating FECD. |
format | Online Article Text |
id | pubmed-8807987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-88079872022-02-08 Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy Wang, Qun Dou, Shengqian Zhang, Bin Jiang, Hui Qi, Xia Duan, Haoyun Wang, Xin Dong, Chunxiao Zhang, Bi Ning Xie, Lixin Cao, Yihai Zhou, Qingjun Shi, Weiyun Mol Ther Nucleic Acids Original Article The corneal endothelium is critical for maintaining corneal clarity by mediating hydration through barrier and pump functions. Progressive loss of corneal endothelial cells during aging has been associated with the development of Fuchs endothelial corneal dystrophy (FECD), one of the main causes of cornea-related vision loss. The mechanisms underlying FECD development remain elusive. Single-cell RNA sequencing of isolated healthy human corneas discovered 4 subpopulations of corneal endothelial cells with distinctive signatures. Unsupervised clustering analysis uncovered nuclear enriched abundant transcript 1 (NEAT1), a long non-coding RNA (lncRNA), as the top expressed gene in the C0-endothelial subpopulation, but markedly downregulated in FECD. Consistent with human corneas, a UVA-induced mouse FECD model validated the loss of NEAT1 expression. Loss of NEAT1 function by an in vivo genetic approach reproduced the exacerbated phenotype of FECD by ablating corneal endothelial cells. Conversely, gain of function by a CRISPR-activated adenoviral delivery system protected corneas from UVA-induced FECD. Our findings provide novel mechanistic insights into the development of FECD, and targeting NEAT1 offers an attractive approach for treating FECD. American Society of Gene & Cell Therapy 2022-01-10 /pmc/articles/PMC8807987/ /pubmed/35141048 http://dx.doi.org/10.1016/j.omtn.2022.01.005 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Wang, Qun Dou, Shengqian Zhang, Bin Jiang, Hui Qi, Xia Duan, Haoyun Wang, Xin Dong, Chunxiao Zhang, Bi Ning Xie, Lixin Cao, Yihai Zhou, Qingjun Shi, Weiyun Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy |
title | Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy |
title_full | Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy |
title_fullStr | Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy |
title_full_unstemmed | Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy |
title_short | Heterogeneity of human corneal endothelium implicates lncRNA NEAT1 in Fuchs endothelial corneal dystrophy |
title_sort | heterogeneity of human corneal endothelium implicates lncrna neat1 in fuchs endothelial corneal dystrophy |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8807987/ https://www.ncbi.nlm.nih.gov/pubmed/35141048 http://dx.doi.org/10.1016/j.omtn.2022.01.005 |
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