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

近视是由于眼睛太长。它是一种常见的屈光不正，影响发达国家约25-30%的人，并导致远视力模糊。大多数近视都很容易用眼镜或隐形眼镜矫正。然而，一小部分人，但重要的是，他们有过长的眼睛和极度的近视。这些放大的眼睛对内部结构施加异常应力，特别是影响视网膜，视网膜是眼睛的感光部分。目前，这些眼睛的视网膜发生的任何损伤都是无法治疗和不可逆的，并可能导致失明。事实上，近视是工作年龄成年人失明的第二大原因。为了使眼睛长得如此之大，它的白色外被膜（巩膜）必须扩张，而不允许任何脆弱的结构和内部液体泄漏。虽然巩膜在扩张时变得非常薄，但已经表明这种扩张过程不仅仅是由于拉伸。在任何拉伸发生之前，巩膜的生化结构必须改变。一个复杂的过程，包括结构成分的合成和分解这些结构成分的酶的活性，在快速放大的眼睛的巩膜中起作用。该项目的目的是干预已经被证明与眼睛过度放大有关的生化过程。我们将使用治疗药物和创新的基因治疗技术来逆转快速放大的眼睛巩膜中发生的生化变化。我们预测，这些疗法将导致巩膜更耐拉伸，眼睛的病理学程度更低。这项研究的结果将为我们提供治疗过度放大的眼睛的潜在治疗策略，从而为我们提供预防许多高度近视个体失明的机会。

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.