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Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification

Posterior capsule opacification (PCO) is a frequent complication after cataract surgery, and advanced PCO requires YAG laser (Nd: YAG) capsulotomy, which often gives rise to more complications. Lens epithelial cell (LEC) proliferation and transformation (i.e., epithelial–mesenchymal transition (EMT)...

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Autores principales: Wei, Zongbo, Gordon, Pasley, Hao, Caili, Huangfu, Jingru, Fan, Emily, Zhang, Xiang, Yan, Hong, Fan, Xingjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265589/
https://www.ncbi.nlm.nih.gov/pubmed/35805085
http://dx.doi.org/10.3390/cells11132001
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author Wei, Zongbo
Gordon, Pasley
Hao, Caili
Huangfu, Jingru
Fan, Emily
Zhang, Xiang
Yan, Hong
Fan, Xingjun
author_facet Wei, Zongbo
Gordon, Pasley
Hao, Caili
Huangfu, Jingru
Fan, Emily
Zhang, Xiang
Yan, Hong
Fan, Xingjun
author_sort Wei, Zongbo
collection PubMed
description Posterior capsule opacification (PCO) is a frequent complication after cataract surgery, and advanced PCO requires YAG laser (Nd: YAG) capsulotomy, which often gives rise to more complications. Lens epithelial cell (LEC) proliferation and transformation (i.e., epithelial–mesenchymal transition (EMT)) are two critical elements in PCO initiation and progression pathogenesis. While PCO marginally impacts aged cataract surgery patients, PCO incidences are exceptionally high in infants and children undergoing cataract surgery. The gene expression of lens epithelial cell aging and its role in the discrepancy of PCO prevalence between young and older people have not been fully studied. Here, we conducted a comprehensive differentially expressed gene (DEG) analysis of a cell aging model by comparing the early and late passage FHL124 lens epithelial cells (LECs). In vitro, TGFβ2, cell treatment, and in vivo mouse cataract surgical models were used to validate our findings. We found that aged LECs decelerated rates of cell proliferation accompanied by dysregulation of cellular immune response and cell stress response. Surprisingly, we found that LECs systematically downregulated epithelial–mesenchymal transition (EMT)-promoting genes. The protein expression of several EMT hallmark genes, e.g., fibronectin, αSMA, and cadherin 11, were gradually decreased during LECs aging. We then confirmed these findings in vitro and found that aged LECs markedly alleviated TGFβ2-mediated EMT. Importantly, we explicitly confirmed the in vitro findings from the in vivo mouse cataract surgery studies. We propose that both the high proliferation rate and EMT-enriched young LECs phenotypic characteristics contribute to unusually high PCO incidence in infants and children.
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spelling pubmed-92655892022-07-09 Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification Wei, Zongbo Gordon, Pasley Hao, Caili Huangfu, Jingru Fan, Emily Zhang, Xiang Yan, Hong Fan, Xingjun Cells Article Posterior capsule opacification (PCO) is a frequent complication after cataract surgery, and advanced PCO requires YAG laser (Nd: YAG) capsulotomy, which often gives rise to more complications. Lens epithelial cell (LEC) proliferation and transformation (i.e., epithelial–mesenchymal transition (EMT)) are two critical elements in PCO initiation and progression pathogenesis. While PCO marginally impacts aged cataract surgery patients, PCO incidences are exceptionally high in infants and children undergoing cataract surgery. The gene expression of lens epithelial cell aging and its role in the discrepancy of PCO prevalence between young and older people have not been fully studied. Here, we conducted a comprehensive differentially expressed gene (DEG) analysis of a cell aging model by comparing the early and late passage FHL124 lens epithelial cells (LECs). In vitro, TGFβ2, cell treatment, and in vivo mouse cataract surgical models were used to validate our findings. We found that aged LECs decelerated rates of cell proliferation accompanied by dysregulation of cellular immune response and cell stress response. Surprisingly, we found that LECs systematically downregulated epithelial–mesenchymal transition (EMT)-promoting genes. The protein expression of several EMT hallmark genes, e.g., fibronectin, αSMA, and cadherin 11, were gradually decreased during LECs aging. We then confirmed these findings in vitro and found that aged LECs markedly alleviated TGFβ2-mediated EMT. Importantly, we explicitly confirmed the in vitro findings from the in vivo mouse cataract surgery studies. We propose that both the high proliferation rate and EMT-enriched young LECs phenotypic characteristics contribute to unusually high PCO incidence in infants and children. MDPI 2022-06-22 /pmc/articles/PMC9265589/ /pubmed/35805085 http://dx.doi.org/10.3390/cells11132001 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wei, Zongbo
Gordon, Pasley
Hao, Caili
Huangfu, Jingru
Fan, Emily
Zhang, Xiang
Yan, Hong
Fan, Xingjun
Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification
title Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification
title_full Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification
title_fullStr Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification
title_full_unstemmed Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification
title_short Aged Lens Epithelial Cells Suppress Proliferation and Epithelial–Mesenchymal Transition-Relevance for Posterior Capsule Opacification
title_sort aged lens epithelial cells suppress proliferation and epithelial–mesenchymal transition-relevance for posterior capsule opacification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265589/
https://www.ncbi.nlm.nih.gov/pubmed/35805085
http://dx.doi.org/10.3390/cells11132001
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