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The Immediate Early Response of Lens Epithelial Cells to Lens Injury

Cataracts are treated by lens fiber cell removal followed by intraocular lens (IOL) implantation into the lens capsule. While effective, this procedure leaves behind numerous lens epithelial cells (LECs) which undergo a wound healing response that frequently leads to posterior capsular opacification...

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Autores principales: Novo, Samuel G., Faranda, Adam P., Shihan, Mahbubul H., Wang, Yan, Garg, Ananya, Duncan, Melinda K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654717/
https://www.ncbi.nlm.nih.gov/pubmed/36359852
http://dx.doi.org/10.3390/cells11213456
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author Novo, Samuel G.
Faranda, Adam P.
Shihan, Mahbubul H.
Wang, Yan
Garg, Ananya
Duncan, Melinda K.
author_facet Novo, Samuel G.
Faranda, Adam P.
Shihan, Mahbubul H.
Wang, Yan
Garg, Ananya
Duncan, Melinda K.
author_sort Novo, Samuel G.
collection PubMed
description Cataracts are treated by lens fiber cell removal followed by intraocular lens (IOL) implantation into the lens capsule. While effective, this procedure leaves behind numerous lens epithelial cells (LECs) which undergo a wound healing response that frequently leads to posterior capsular opacification (PCO). In order to elucidate the acute response of LECs to lens fiber cell removal which models cataract surgery (post cataract surgery, PCS), RNA-seq was conducted on LECs derived from wild type mice at 0 and 6 h PCS. This analysis found that LECs upregulate the expression of numerous proinflammatory cytokines and profibrotic regulators by 6 h PCS suggesting rapid priming of pathways leading to inflammation and fibrosis PCS. LECs also highly upregulate the expression of numerous immediate early transcription factors (IETFs) by 6 h PCS and immunolocalization found elevated levels of these proteins by 3 h PCS, and this was preceded by the phosphorylation of ERK1/2 in injured LECs. Egr1 and FosB were among the highest expressed of these factors and qRT-PCR revealed that they also upregulate in explanted mouse lens epithelia suggesting potential roles in the LEC injury response. Analysis of lenses lacking either Egr1 or FosB revealed that both genes may regulate a portion of the acute LEC injury response, although neither gene was essential for expression of either proinflammatory or fibrotic markers at later times PCS suggesting that IETFs may work in concert to mediate the LEC injury response following cataract surgery.
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spelling pubmed-96547172022-11-15 The Immediate Early Response of Lens Epithelial Cells to Lens Injury Novo, Samuel G. Faranda, Adam P. Shihan, Mahbubul H. Wang, Yan Garg, Ananya Duncan, Melinda K. Cells Article Cataracts are treated by lens fiber cell removal followed by intraocular lens (IOL) implantation into the lens capsule. While effective, this procedure leaves behind numerous lens epithelial cells (LECs) which undergo a wound healing response that frequently leads to posterior capsular opacification (PCO). In order to elucidate the acute response of LECs to lens fiber cell removal which models cataract surgery (post cataract surgery, PCS), RNA-seq was conducted on LECs derived from wild type mice at 0 and 6 h PCS. This analysis found that LECs upregulate the expression of numerous proinflammatory cytokines and profibrotic regulators by 6 h PCS suggesting rapid priming of pathways leading to inflammation and fibrosis PCS. LECs also highly upregulate the expression of numerous immediate early transcription factors (IETFs) by 6 h PCS and immunolocalization found elevated levels of these proteins by 3 h PCS, and this was preceded by the phosphorylation of ERK1/2 in injured LECs. Egr1 and FosB were among the highest expressed of these factors and qRT-PCR revealed that they also upregulate in explanted mouse lens epithelia suggesting potential roles in the LEC injury response. Analysis of lenses lacking either Egr1 or FosB revealed that both genes may regulate a portion of the acute LEC injury response, although neither gene was essential for expression of either proinflammatory or fibrotic markers at later times PCS suggesting that IETFs may work in concert to mediate the LEC injury response following cataract surgery. MDPI 2022-11-01 /pmc/articles/PMC9654717/ /pubmed/36359852 http://dx.doi.org/10.3390/cells11213456 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
Novo, Samuel G.
Faranda, Adam P.
Shihan, Mahbubul H.
Wang, Yan
Garg, Ananya
Duncan, Melinda K.
The Immediate Early Response of Lens Epithelial Cells to Lens Injury
title The Immediate Early Response of Lens Epithelial Cells to Lens Injury
title_full The Immediate Early Response of Lens Epithelial Cells to Lens Injury
title_fullStr The Immediate Early Response of Lens Epithelial Cells to Lens Injury
title_full_unstemmed The Immediate Early Response of Lens Epithelial Cells to Lens Injury
title_short The Immediate Early Response of Lens Epithelial Cells to Lens Injury
title_sort immediate early response of lens epithelial cells to lens injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9654717/
https://www.ncbi.nlm.nih.gov/pubmed/36359852
http://dx.doi.org/10.3390/cells11213456
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