The ultrastructural basis of corneal dysfunction and the development and optimization of novel therapeutic strategies

角膜功能障碍的超微结构基础及新型治疗策略的开发和优化

基本信息

批准号：
MR/K000837/1
负责人：
Keith Meek
金额：
$ 223.59万
依托单位：
CARDIFF UNIVERSITY
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FK000837%2F1
关键词：
ultrastructural basis corneal dysfunction development

项目摘要

The cornea is the transparent window at the front of the eye and is its main focussing element. To fulfil its role it has to be very transparent, very strong and precisely shaped. Transparency, strength and shape are all controlled by the collagen fibrils that make up the cornea, and by the small molecules between them. This happens at different structural levels from the molecular level upwards: collagen molecules form fibrils, which in turn form larger structures called lamellae, which are then stacked up to form the tissue itself. From our previous work and work done by others, we know a lot about why the cornea is transparent and are beginning to understand the arrangement of collagen lamellae that gives rise to the cornea's shape and thus its focusing abilities. However, the precise details are still not known and, until they are, it will not be possible to understand why, in numerous diseases of the cornea, or after different types of surgery on the cornea - including laser surgery - transparency, strength and/or shape are abnormal and vision is lost or very blurred. We will use several new and exciting 3-D biological imaging and powerful X-ray measuring techniques, to explain how collagen fibrils and cells are arranged in the cornea to make it transparent, and how other proteins control this arrangement. We will also explain at a higher structural level how lamellae are arranged to provide form and strength. This will allow us to construct computer models from which to predict changes in corneal shape following given surgical incisions or other treatments to help inform surgeons. We will then explain what goes wrong in several important corneal diseases and investigate methods of preventing or correcting these changes, for example by using stem cell therapy or protein crosslinking. The methods will also allow us to explain why, when the cornea is wounded, tissue strength and transparency are compromised. Again, methods to improve this wound healing such as those mentioned above will be investigated, with the aim of strengthening the cornea whilst preserving transparency. Finally, several research groups in different countries are trying to develop a biological artificial cornea as there is, and is likely to continue to be, a worldwide shortage of donor corneal tissue for graft surgery. Synthetic biology depends on understanding how nature utilises the constituents of a tissue to achieve its vital properties. In the case of the cornea, the knowledge that we will obtain by elucidating the exact relationship between structure and function will be invaluable, and will allow us to collaborate with these groups to drive their constructs more quickly towards a fully functioning artificial cornea.

角膜是眼前的透明窗口，是其主要集中元素。要履行其角色，它必须非常透明，非常强大且精确地形状。透明度，强度和形状均由构成角膜的胶原原纤维以及它们之间的小分子控制。这发生在不同的结构水平与分子水平的不同水平上：胶原蛋白分子形成原纤维，从而形成了称为薄片的较大结构，然后将其堆叠起来以形成组织本身。从我们以前的工作和工作的工作中，我们了解了为什么角膜是透明的，并且开始理解胶原板层的布置，从而产生了角膜的形状，从而产生了其聚焦能力。但是，精确的细节仍然不知道，直到它们是在角膜多种疾病中，或者在角膜上的不同类型的手术（包括激光手术）上（包括激光手术） - 透明度，强度和/或形状异常，视力丧失或非常模糊的原因，这将无法理解为什么在许多类型的角膜手术后（包括激光手术），因此无法理解为什么要理解为什么确切的细节 - 无法确切的细节，因此，确切细节仍然不清楚，因此，确切细节仍然不清楚，因此，确切细节仍然不清楚，透明度和视力是丢失，因此，因此，为什么不可能理解为什么，透明和/丢失了后，因此，为什么不可能理解为什么我们将使用几种新的且令人兴奋的3-D生物成像和功能强大的X射线测量技术，以解释如何在角膜中排列胶原蛋白原纤维和细胞，以使其透明，以及其他蛋白质如何控制这种布置。我们还将在更高的结构层面解释如何布置薄片以提供形式和强度。这将使我们能够构建计算机模型，从中可以从中预测出手术切口或其他治疗后角膜形状的变化，以帮助外科医生通知外科医生。然后，我们将解释几种重要的角膜疾病中出了什么问题，并研究预防或纠正这些变化的方法，例如使用干细胞疗法或蛋白质交联。这些方法还将使我们能够解释为什么当角膜受伤时，组织强度和透明度会受到损害。同样，将研究改善这种伤口愈合的方法，例如上述愈合，以增强角膜，同时保持透明度。最后，不同国家的几个研究小组正试图像以前（并可能继续存在）在全球范围内缺乏用于移植手术的供体角膜组织短缺的生物人造角膜。合成生物学取决于理解自然如何利用组织的成分来实现其重要特性。在角膜的情况下，我们将通过阐明结构和功能之间的确切关系而获得的知识是无价的，并且将使我们能够与这些群体合作，以更快地将其构造驱动到功能齐全的人造角膜。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Standard versus accelerated riboflavin-ultraviolet corneal collagen crosslinking: Resistance against enzymatic digestion.

DOI：
10.1016/j.jcrs.2015.10.004
发表时间：
2015-09
期刊：
Journal of cataract and refractive surgery
影响因子：
2.8
作者：
Aldahlawi NH;Hayes S;O'Brart DP;Meek KM
通讯作者：
Meek KM

Tropocollagen springs allow collagen fibrils to stretch elastically.

DOI：
10.1016/j.actbio.2022.01.041
发表时间：
2022-04-01
期刊：
Acta biomaterialia
影响因子：
9.7
作者：
Bell JS;Hayes S;Whitford C;Sanchez-Weatherby J;Shebanova O;Terrill NJ;Sørensen TLM;Elsheikh A;Meek KM
通讯作者：
Meek KM

An investigation into corneal enzymatic resistance following epithelium-off and epithelium-on corneal cross-linking protocols.

DOI：
10.1016/j.exer.2016.10.014
发表时间：
2016-12
期刊：
EXPERIMENTAL EYE RESEARCH
影响因子：
3.4
作者：
Aldahlawi, Nada H.;Hayes, Sally;O'Brart, David P. S.;O'Brart, Naomi D.;Meek, Keith M.
通讯作者：
Meek, Keith M.

Clinical and laboratory investigation of the biomechanical properties of the cornea