Mulholland, Bridget; (2000) The role of matrix metalloproteinases in corneal wound healing. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Corneal Scarring is a major cause of visual loss. In the developing world the commonest causes are trachoma, trauma, infection and nutritional deficiency. In developed regions the major causes are herpetic eye disease and trauma. With the increasing demand for corneal refractive surgery, healing without scarring has become a major issue, particularly as the surgery is performed on healthy eyes with normal corneas. This thesis has investigated the role of matrix metalloproteinases (MMPs) in the process of corneal wound healing and looked at the potential use of broad spectrum Synthetic Inhibitors of MMPs (SIMPs) in the modulation of healing with a particular emphasis on scar tissue deposition. The histological changes in corneal wounds and development of scar tissue was examined after superficial keratectomy in a rabbit. After corneal wounding, MMP-1 and -9 expression was found to be associated with re-epithelialisation and MMP-2 with stromal re-modelling. Broad spectrum SIMPs were found to reduce migration of rabbit corneal epithelial cells and fibroblasts on collagen type I in vitro. The toxicity of two broad spectrum SIMPs on the rabbit eye was examined in vivo. Topically applied broad spectrum SIMP caused a reversible inhibition of re-epithelialisation and reduction of scarring at 45 days in the rabbit superficial keratectomy model in vivo. An objective method for the assessment of corneal scarring enabled comparison of various potential anti-scarring treatments in vivo. The results indicate that broad spectrum SIMPs may not be appropriate clinically in the modulation of corneal scarring due to the effect on re-epithelialisation of corneal wounds. However, there may be a role for more specific inhibitors of MMPs.

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