Therapeutic regulation of matrix metabolism to stabilise the biomechanical properties of the sclera in high myopia

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Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light sensitive part of the eye. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order for the eye to grow so large its white, outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change. A complex process, involving the synthesis of structural components and the activity of enzymes that breakdown these structural components, is at work in the sclera of eyes that are rapidly enlarging. The aim of this project is to intervene in the biochemical processes that have already been shown to be involved in excessive eye enlargement. We will use both therapeutic agents and innovative gene therapy techniques to reverse the biochemical changes that occur in the sclera of rapidly enlarging eyes. We predict that these therapies will result in a sclera that is more resistant to being stretched and an eye that has less pathology. The results from this study will provide us with potential therapeutic strategies for the treatment of eyes that are enlarging excessively, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.