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NPJ Regen Med. 2018 Dec 21;3:23. doi: 10.1038/s41536-018-0061-4. eCollection 2018.

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

Author information

1
1Institute of Clinical Sciences, University of Birmingham, Birmingham, B15 2TH UK.
2
2School of Chemical Engineering, University of Birmingham, Birmingham, B15 2TT UK.
3
3Department of Ophthalmology, University of California, Irvine, CA 92612 USA.
4
4Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TT UK.
5
5Birmingham and Midland Eye Centre, SWBH NHS Trust, Birmingham, B18 7QH UK.
6
6Diagnostics, Drugs, Devices and Biomarkers clinical trials team (D3B), Institute for Translational Medicine, University of Birmingham, Birmingham, B15 2TT UK.
#
Contributed equally

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 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.

Conflict of interest statement

The authors declare no competing interests.

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