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Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration
The cornea of the eye is at risk for injury through constant exposure to the extraocular environment. A highly collagenous structure, the cornea contains several different types distributed across multiple layers. The anterior-most layer contains non-keratinized epithelial cells that serve as a barr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415399/ https://www.ncbi.nlm.nih.gov/pubmed/34483909 http://dx.doi.org/10.3389/fphar.2021.705623 |
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author | Baratta, Robert O. Del Buono, Brian J. Schlumpf, Eric Ceresa, Brian P. Calkins, David J. |
author_facet | Baratta, Robert O. Del Buono, Brian J. Schlumpf, Eric Ceresa, Brian P. Calkins, David J. |
author_sort | Baratta, Robert O. |
collection | PubMed |
description | The cornea of the eye is at risk for injury through constant exposure to the extraocular environment. A highly collagenous structure, the cornea contains several different types distributed across multiple layers. The anterior-most layer contains non-keratinized epithelial cells that serve as a barrier to environmental, microbial, and other insults. Renewal and migration of basal epithelial cells from the limbus involve critical interactions between secreted basement membranes, composed primarily of type IV collagen, and underlying Bowman’s and stromal layers, which contain primarily type I collagen. This process is challenged in many diseases and conditions that insult the ocular surface and damage underlying collagen. We investigated the capacity of a collagen mimetic peptide (CMP), representing a fraction of a single strand of the damaged triple helix human type I collagen, to promote epithelial healing following an acute corneal wound. In vitro, the collagen mimetic peptide promoted the realignment of collagen damaged by enzymic digestion. In an in vivo mouse model, topical application of a CMP-containing formulation following a 360° lamellar keratectomy targeting the corneal epithelial layer accelerated wound closure during a 24 h period, compared to vehicle. We found that the CMP increased adherence of the basal epithelium to the underlying substrate and enhanced density of epithelial cells, while reducing variability in the regenerating layer. These results suggest that CMPs may represent a novel therapeutic to heal corneal tissue by repairing underlying collagen in conditions that damage the ocular surface. |
format | Online Article Text |
id | pubmed-8415399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84153992021-09-04 Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration Baratta, Robert O. Del Buono, Brian J. Schlumpf, Eric Ceresa, Brian P. Calkins, David J. Front Pharmacol Pharmacology The cornea of the eye is at risk for injury through constant exposure to the extraocular environment. A highly collagenous structure, the cornea contains several different types distributed across multiple layers. The anterior-most layer contains non-keratinized epithelial cells that serve as a barrier to environmental, microbial, and other insults. Renewal and migration of basal epithelial cells from the limbus involve critical interactions between secreted basement membranes, composed primarily of type IV collagen, and underlying Bowman’s and stromal layers, which contain primarily type I collagen. This process is challenged in many diseases and conditions that insult the ocular surface and damage underlying collagen. We investigated the capacity of a collagen mimetic peptide (CMP), representing a fraction of a single strand of the damaged triple helix human type I collagen, to promote epithelial healing following an acute corneal wound. In vitro, the collagen mimetic peptide promoted the realignment of collagen damaged by enzymic digestion. In an in vivo mouse model, topical application of a CMP-containing formulation following a 360° lamellar keratectomy targeting the corneal epithelial layer accelerated wound closure during a 24 h period, compared to vehicle. We found that the CMP increased adherence of the basal epithelium to the underlying substrate and enhanced density of epithelial cells, while reducing variability in the regenerating layer. These results suggest that CMPs may represent a novel therapeutic to heal corneal tissue by repairing underlying collagen in conditions that damage the ocular surface. Frontiers Media S.A. 2021-08-16 /pmc/articles/PMC8415399/ /pubmed/34483909 http://dx.doi.org/10.3389/fphar.2021.705623 Text en Copyright © 2021 Baratta, Del Buono, Schlumpf, Ceresa and Calkins. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Baratta, Robert O. Del Buono, Brian J. Schlumpf, Eric Ceresa, Brian P. Calkins, David J. Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration |
title | Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration |
title_full | Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration |
title_fullStr | Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration |
title_full_unstemmed | Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration |
title_short | Collagen Mimetic Peptides Promote Corneal Epithelial Cell Regeneration |
title_sort | collagen mimetic peptides promote corneal epithelial cell regeneration |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415399/ https://www.ncbi.nlm.nih.gov/pubmed/34483909 http://dx.doi.org/10.3389/fphar.2021.705623 |
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