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

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@article{c9faa90eadae4327a447f2f9a0d1068f,
title = "Sustained release of decorin to the surface of the eye enables scarless corneal regeneration",
abstract = "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 Pseudomonaskeratitis, 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.",
author = "Hill, {Lisa Jayne} and Richard Moakes and Chairut Vareechon and Gibran Butt and Aaron Ng and Kristian Brock and Gurpreet Chouhan and Rachel Vincent and Serena Abbondante and Richard Williams and Nicholas Barnes and Eric Pearlman and Graham Wallace and Saaeha Rauz and Ann Logan and Liam Grover",
year = "2018",
month = dec,
day = "21",
doi = "10.1038/s41536-018-0061-4",
language = "English",
volume = "3",
journal = "npj Regenerative Medicine",
issn = "2057-3995",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Sustained release of decorin to the surface of the eye enables scarless corneal regeneration

AU - Hill, Lisa Jayne

AU - Moakes, Richard

AU - Vareechon, Chairut

AU - Butt, Gibran

AU - Ng, Aaron

AU - Brock, Kristian

AU - Chouhan, Gurpreet

AU - Vincent, Rachel

AU - Abbondante, Serena

AU - Williams, Richard

AU - Barnes, Nicholas

AU - Pearlman, Eric

AU - Wallace, Graham

AU - Rauz, Saaeha

AU - Logan, Ann

AU - Grover, Liam

PY - 2018/12/21

Y1 - 2018/12/21

N2 - 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 Pseudomonaskeratitis, 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.

AB - 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 Pseudomonaskeratitis, 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.

U2 - 10.1038/s41536-018-0061-4

DO - 10.1038/s41536-018-0061-4

M3 - Article

C2 - 30588331

VL - 3

JO - npj Regenerative Medicine

JF - npj Regenerative Medicine

SN - 2057-3995

M1 - 23

ER -