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Sustained release of decorin to the surface of the eye enables scarless corneal regeneration

Disorganization of the transparent collagenous matrix in the cornea, as a consequence of a variety of infections and inflammatory conditions, leads to corneal opacity and sight-loss. Such corneal opacities are a leading cause of blindness, according to the WHO. Public health programs target preventi...

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Autores principales: Hill, Lisa J., Moakes, Richard J. A., Vareechon, Chairut, Butt, Gibran, Ng, Aaron, Brock, Kristian, Chouhan, Gurpreet, Vincent, Rachel C., Abbondante, Serena, Williams, Richard L., Barnes, Nicholas M., Pearlman, Eric, Wallace, Graham R., Rauz, Saaeha, Logan, Ann, Grover, Liam M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303295/
https://www.ncbi.nlm.nih.gov/pubmed/30588331
http://dx.doi.org/10.1038/s41536-018-0061-4
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author Hill, Lisa J.
Moakes, Richard J. A.
Vareechon, Chairut
Butt, Gibran
Ng, Aaron
Brock, Kristian
Chouhan, Gurpreet
Vincent, Rachel C.
Abbondante, Serena
Williams, Richard L.
Barnes, Nicholas M.
Pearlman, Eric
Wallace, Graham R.
Rauz, Saaeha
Logan, Ann
Grover, Liam M.
author_facet Hill, Lisa J.
Moakes, Richard J. A.
Vareechon, Chairut
Butt, Gibran
Ng, Aaron
Brock, Kristian
Chouhan, Gurpreet
Vincent, Rachel C.
Abbondante, Serena
Williams, Richard L.
Barnes, Nicholas M.
Pearlman, Eric
Wallace, Graham R.
Rauz, Saaeha
Logan, Ann
Grover, Liam M.
author_sort Hill, Lisa J.
collection PubMed
description Disorganization of the transparent collagenous matrix in the cornea, as a consequence of a variety of infections and inflammatory conditions, leads to corneal opacity and sight-loss. Such corneal opacities are a leading cause of blindness, according to the WHO. Public health programs target prevention of corneal scarring, but the only curative treatment of established scarring is through transplantation. Although attempts to minimize corneal scarring through aggressive control of infection and inflammation are made, there has been little progress in the development of anti-scarring therapies. This is owing to eye drop formulations using low viscosity or weak gelling materials having short retention times on the ocular surface. In this study, we report an innovative eye drop formulation that has the ability to provide sustained delivery of decorin, an anti-scarring agent. The novelty of this eye drop lies in the method of structuring during manufacture, which creates a material that can transition between solid and liquid states, allowing retention in a dynamic environment being slowly removed through blinking. In a murine model of Pseudomonas keratitis, applying the eye drop resulted in reductions of corneal opacity within 16 days. More remarkably, the addition of hrDecorin resulted in restoration of corneal epithelial integrity with minimal stromal opacity endorsed by reduced α-smooth muscle actin (αSMA), fibronectin, and laminin levels. We believe that this drug delivery system is an ideal non-invasive anti-fibrotic treatment for patients with microbial keratitis, potentially without recourse to surgery, saving the sight of many in the developing world, where corneal transplantation may not be available.
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spelling pubmed-63032952018-12-26 Sustained release of decorin to the surface of the eye enables scarless corneal regeneration Hill, Lisa J. Moakes, Richard J. A. Vareechon, Chairut Butt, Gibran Ng, Aaron Brock, Kristian Chouhan, Gurpreet Vincent, Rachel C. Abbondante, Serena Williams, Richard L. Barnes, Nicholas M. Pearlman, Eric Wallace, Graham R. Rauz, Saaeha Logan, Ann Grover, Liam M. NPJ Regen Med Article Disorganization of the transparent collagenous matrix in the cornea, as a consequence of a variety of infections and inflammatory conditions, leads to corneal opacity and sight-loss. Such corneal opacities are a leading cause of blindness, according to the WHO. Public health programs target prevention of corneal scarring, but the only curative treatment of established scarring is through transplantation. Although attempts to minimize corneal scarring through aggressive control of infection and inflammation are made, there has been little progress in the development of anti-scarring therapies. This is owing to eye drop formulations using low viscosity or weak gelling materials having short retention times on the ocular surface. In this study, we report an innovative eye drop formulation that has the ability to provide sustained delivery of decorin, an anti-scarring agent. The novelty of this eye drop lies in the method of structuring during manufacture, which creates a material that can transition between solid and liquid states, allowing retention in a dynamic environment being slowly removed through blinking. In a murine model of Pseudomonas keratitis, applying the eye drop resulted in reductions of corneal opacity within 16 days. More remarkably, the addition of hrDecorin resulted in restoration of corneal epithelial integrity with minimal stromal opacity endorsed by reduced α-smooth muscle actin (αSMA), fibronectin, and laminin levels. We believe that this drug delivery system is an ideal non-invasive anti-fibrotic treatment for patients with microbial keratitis, potentially without recourse to surgery, saving the sight of many in the developing world, where corneal transplantation may not be available. Nature Publishing Group UK 2018-12-21 /pmc/articles/PMC6303295/ /pubmed/30588331 http://dx.doi.org/10.1038/s41536-018-0061-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hill, Lisa J.
Moakes, Richard J. A.
Vareechon, Chairut
Butt, Gibran
Ng, Aaron
Brock, Kristian
Chouhan, Gurpreet
Vincent, Rachel C.
Abbondante, Serena
Williams, Richard L.
Barnes, Nicholas M.
Pearlman, Eric
Wallace, Graham R.
Rauz, Saaeha
Logan, Ann
Grover, Liam M.
Sustained release of decorin to the surface of the eye enables scarless corneal regeneration
title Sustained release of decorin to the surface of the eye enables scarless corneal regeneration
title_full Sustained release of decorin to the surface of the eye enables scarless corneal regeneration
title_fullStr Sustained release of decorin to the surface of the eye enables scarless corneal regeneration
title_full_unstemmed Sustained release of decorin to the surface of the eye enables scarless corneal regeneration
title_short Sustained release of decorin to the surface of the eye enables scarless corneal regeneration
title_sort sustained release of decorin to the surface of the eye enables scarless corneal regeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303295/
https://www.ncbi.nlm.nih.gov/pubmed/30588331
http://dx.doi.org/10.1038/s41536-018-0061-4
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