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The effect of cell-based therapy on LASIK-like corneal wounds

Phillips, Camilla 2018. The effect of cell-based therapy on LASIK-like corneal wounds. PhD Thesis, Cardiff University.
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Abstract

The aim of this study was to determine if oral mucosal lamina propria progenitor cell (OMLP-PC)-based therapy to the stromal beds of LASIK-like wounded corneas could improve wound healing. After epithelial and/or stromal injury, a wound healing cascade is triggered that includes keratocyte apoptosis and proliferation in the underlying stroma. Activation of keratocytes leads to their transformation into myofibroblasts, which are responsible for matrix remodelling. Unfortunately, LASIK-like wound healing can result in incomplete closure at the flap interface, reduced biomechanical strength and decreased transparency. The hypothesis of this study was that a therapeutic application of OMLP-PCs, known to facilitate non-scarring healing, to the corneal wound bed, would reduce keratocyte activation and consequent myofibroblastic transformation to augment matrix remodelling and restore transparency. To test this hypothesis, a corneal organ culture model was developed to monitor LASIK-like wound healing outcomes. The efficacy of a cell-based therapy, namely OMLP-PCs, on LASIK-like wound healing was evaluated and optimised over four weeks. The wound healing outcomes of the organ cultured porcine corneas included a significant reduction of percentage α-sma immunopositive cells (p<0.01) from ~45% (untreated wounded) to ~25% (OMLP-PC-treated) during weeks 2-3 post wounding. Peak percentage proliferation was 52.2% ±3.7 at 1 week in OMLP-PC treated wounds, earlier compared to 42.2% ±3.3 at 2 weeks in untreated control corneas. OMLP-PCs did not alter stromal percentage apoptosis. Coherence (degree of collagen lamellae alignment) at 4 weeks after wound healing was significantly higher in OMLP-PC treated wounded corneas (p<0.05), compared to that in untreated corneas. By 4 weeks corneal transparency in OMLP-PC treated wounded corneas was significantly higher than in untreated corneas (p<0.01). To conclude, an OMLP-PC therapeutic application to LASIK-like wounds enhanced stromal cell proliferation and reduced myofibroblast expression, but increased collagen organisation with consequent improved epithelial-stromal flap wound closure and increased corneal transparency.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: Cornea, Wound healing, Refractive Surgery, OMLP-PC, Keratocytes, Collagen, LASIK
Funders: Engineering and Physical Sciences Research Council
Date of First Compliant Deposit: 7 May 2019
Last Modified: 03 May 2020 02:05
URI: http://orca.cf.ac.uk/id/eprint/122160

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