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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...

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Autores principales: Baratta, Robert O., Del Buono, Brian J., Schlumpf, Eric, Ceresa, Brian P., Calkins, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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.
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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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