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LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis
The cornea requires constant epithelial renewal to maintain clarity for appropriate vision. A subset of stem cells residing at the limbus is primarily responsible for maintaining corneal epithelium homeostasis. Trauma and disease may lead to stem cell deficiency and therapeutic targeting to replenis...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834794/ https://www.ncbi.nlm.nih.gov/pubmed/26661907 http://dx.doi.org/10.1002/stem.2257 |
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author | Sartaj, Rachel Chee, Ru‐ik Yang, Jing Wan, Pengxia Liu, Aihong Guaiquil, Victor Fuchs, Elaine Rosenblatt, Mark I. |
author_facet | Sartaj, Rachel Chee, Ru‐ik Yang, Jing Wan, Pengxia Liu, Aihong Guaiquil, Victor Fuchs, Elaine Rosenblatt, Mark I. |
author_sort | Sartaj, Rachel |
collection | PubMed |
description | The cornea requires constant epithelial renewal to maintain clarity for appropriate vision. A subset of stem cells residing at the limbus is primarily responsible for maintaining corneal epithelium homeostasis. Trauma and disease may lead to stem cell deficiency and therapeutic targeting to replenish the stemness capacity has been stalled by the lack of reliable corneal epithelial stem cell markers. Here we identified the location of Lhx2 in mice (mLhx2) cornea and conjunctival tissue using an Lhx2eGFP reporter model and in human tissues (hLHX2). Lhx2 localized to the basal cells of central cornea, the conjunctiva and the entire limbal epithelium in humans and mice. To ascribe a functional role we generated Lhx2 conditional knockout (cKO) mice and the phenotypic effects in corneas were analyzed by slit lamp microscopy, in cell‐based assays and in a model of corneal epithelium debridement. Immunodetection on corneal sections were used to visualize conjunctivalization, a sign of limbal barrier failure. Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification. Cell based assays showed that Lhx2cKO derived corneal epithelial cells have a significantly lower capacity to form colonies over time and delayed wound‐healing recovery when compared to wildtype cells. Repeated corneal epithelial wounding resulted in decreased re‐epithelialization and multiple cornea lesions in Lhx2cKO mice compared to normal recovery seen in wildtype mice. We conclude that Lhx2 is required for maintenance of the corneal epithelial cell compartment and the limbal barrier. Stem Cells 2016;34:493–503 |
format | Online Article Text |
id | pubmed-4834794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48347942016-05-06 LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis Sartaj, Rachel Chee, Ru‐ik Yang, Jing Wan, Pengxia Liu, Aihong Guaiquil, Victor Fuchs, Elaine Rosenblatt, Mark I. Stem Cells Tissue‐Specific Stem Cells The cornea requires constant epithelial renewal to maintain clarity for appropriate vision. A subset of stem cells residing at the limbus is primarily responsible for maintaining corneal epithelium homeostasis. Trauma and disease may lead to stem cell deficiency and therapeutic targeting to replenish the stemness capacity has been stalled by the lack of reliable corneal epithelial stem cell markers. Here we identified the location of Lhx2 in mice (mLhx2) cornea and conjunctival tissue using an Lhx2eGFP reporter model and in human tissues (hLHX2). Lhx2 localized to the basal cells of central cornea, the conjunctiva and the entire limbal epithelium in humans and mice. To ascribe a functional role we generated Lhx2 conditional knockout (cKO) mice and the phenotypic effects in corneas were analyzed by slit lamp microscopy, in cell‐based assays and in a model of corneal epithelium debridement. Immunodetection on corneal sections were used to visualize conjunctivalization, a sign of limbal barrier failure. Lhx2cKO mice produced reduced body hair and spontaneous epithelial defects in the cornea that included neovascularization, perforation with formation of scar tissue and opacification. Cell based assays showed that Lhx2cKO derived corneal epithelial cells have a significantly lower capacity to form colonies over time and delayed wound‐healing recovery when compared to wildtype cells. Repeated corneal epithelial wounding resulted in decreased re‐epithelialization and multiple cornea lesions in Lhx2cKO mice compared to normal recovery seen in wildtype mice. We conclude that Lhx2 is required for maintenance of the corneal epithelial cell compartment and the limbal barrier. Stem Cells 2016;34:493–503 John Wiley and Sons Inc. 2016-01-05 2016-02 /pmc/articles/PMC4834794/ /pubmed/26661907 http://dx.doi.org/10.1002/stem.2257 Text en © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Tissue‐Specific Stem Cells Sartaj, Rachel Chee, Ru‐ik Yang, Jing Wan, Pengxia Liu, Aihong Guaiquil, Victor Fuchs, Elaine Rosenblatt, Mark I. LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis |
title | LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis |
title_full | LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis |
title_fullStr | LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis |
title_full_unstemmed | LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis |
title_short | LIM Homeobox Domain 2 Is Required for Corneal Epithelial Homeostasis |
title_sort | lim homeobox domain 2 is required for corneal epithelial homeostasis |
topic | Tissue‐Specific Stem Cells |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4834794/ https://www.ncbi.nlm.nih.gov/pubmed/26661907 http://dx.doi.org/10.1002/stem.2257 |
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