A Physical Characterisation of Assembly Mechanisms and Light Transmission in Cornea.

角膜组装机制和光传输的物理表征。

基本信息

批准号：
EP/F034970/1
负责人：
Andrew Quantock
金额：
$ 106.65万
依托单位：
CARDIFF UNIVERSITY
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FF034970%2F1
关键词：
Physical Characterisation Assembly Mechanisms Light

项目摘要

The cornea is the front clear part of the eye. It is essential for proper vision because it lets in light and focuses it on the retina at the back of the eye. Thus, a sharp image is formed and we can see properly. The cornea is a special tissue because it is transparent, and in this respect it is unlike other related tissues in the body -- the tendons that link our bones and muscles or the sclera (the white of the eye), for example -- that are made of similar components. Scientists believe that the cornea is transparent because the protein called collagen that forms much of the cornea is mostly in the form of long, thin rope-like structures called fibrils. Moreover, these collagen fibrils are formed into a very well defined arrangement that lets light through. If this arrangement breaks down the cornea looses its transparency and becomes cloudy. As a result vision is severely compromised.We propose a programme of research that uses new physics-based techniques to investigate the internal fine structure of the cornea and how it develops. We will use the chick cornea as a model system because it has been studied many times before. We will compare our structural data with measurements of corneal transparency that our colleagues in the United States will obtain in conjunction with us. We will also use our techniques to study new artificial corneas that are being made in the laboratory by scientists in Japan; by discovering how the collagen fibrils assemble in the bioengineered cornea compared to in the naturally developing cornea we can help guide efforts to make transparent, functional corneas.First, we will devise new ways of preparing cornea tissue for examination at very high magnification in an electron microscope. These preparation methods will use high-pressure freezing technology so that when placed in the electron microscope thin sections of the cornea will retain native structure much better than after other conventional chemical ways of preparing the tissue. The ultrastructure of collagen fibrils can then be examined at a magnification of up to 50,000 times. This information essential if we are to create mathematical models of why the cornea is transparent. We also point out that the development of this new electron microscopy technique will also be of great use to scientists in other fields who investigate other biological tissues, systems and components.We will also use a technique called x-ray diffraction to study corneal ultrastructure using more focused x-ray beams than have ever been used before to study corneal development. The x-rays we will use will be very intense and produced by synchrotron sources. These are highly specialised, large particle accelerators and we will conduct experiments with colleagues in Japan, in France as well as here in the UK. The data will provide structural information at a much better resolution than has previously been possible. Again, we will link structural data with transparency to understand what makes the cornea transparent.Interestingly, scientists suspect that molecules with sulphate components in the cornea influence the collagen fibrils and force them to take up the special arrangement that allows corneal transparency. Sulphate levels have not been measured directly in cornea previously because this is very difficult to do. We will bring astrophysical spectroscopy expertise ordinarily used in space research to quantify sulphate changes in the cornea as it develops. This will teach us how sulphated molecules control collagen arrangement.Overall, the research will teach us how the cornea assembles itself during development and when it is engineered in the laboratory, and why the cornea is transparent. We will also develop new technologies in biophysics research that other scientists can benefit from.

角膜是眼睛的前部。它对于适当的视力至关重要，因为它可以允许光线并将其聚焦在眼睛背面的视网膜上。因此，形成了尖锐的图像，我们可以正确看到。角膜是一种特殊的组织，因为它是透明的，在这方面，它与体内的其他相关组织不同 - 将我们的骨骼和肌肉或巩膜（例如，眼睛的白色）连接起来，是由相似成分组成的。科学家认为，角膜是透明的，因为形成大部分角膜的蛋白质称为胶原蛋白，主要是以长而细的绳子样结构的形式称为原纤维。此外，这些胶原蛋白原纤维形成了一个非常明确的排列，可以通过。如果这种布置破坏了角膜的透明度并变得多云。结果，视力受到严重损害。我们提出了一项研究计划，该计划使用新的基于物理学的技术研究角膜的内部细胞及其发展方式。我们将使用Chick Cornea作为模型系统，因为它以前已经对其进行了多次研究。我们将将我们的结构数据与我们在美国同事将与我们共同获得的角膜透明度的测量结果进行比较。我们还将使用我们的技术来研究日本科学家在实验室中制造的新人造角膜；通过发现与自然发育的角膜相比，胶原蛋白原纤维如何在生物工程角膜中组装在一起，我们可以帮助指导努力使透明，功能性角膜。首先，我们将设计新的方法来制备角膜组织，以在电子显微镜中非常高放大倍率。这些制备方法将使用高压冰冻技术，因此，将其放在电子显微镜薄层中时，角膜的薄切片将比其他常规化学方法在制备组织的其他化学方法之后保留好得多。然后，可以以高达50,000次的放大倍率检查胶原原纤维的超微结构。如果我们要创建角膜为何透明的数学模型，那么这些信息至关重要。我们还指出，这种新的电子显微镜技术的开发也将对研究其他生物组织，系统和组件的其他领域的科学家有很大的帮助。我们还将使用一种称为X射线衍射的技术来研究角膜超微结构，使用比以前使用更多的X射线束研究角膜射线。我们将使用的X射线将非常激烈，并由同步加速器来源产生。这些是高度专业化的大粒子加速器，我们将在法国和英国与日本以及英国的同事进行实验。该数据将以比以前可能更好的分辨率提供结构信息。同样，我们将将结构数据与透明度联系起来，以了解是什么使角膜透明。科学家怀疑角膜中硫酸盐成分的分子会影响胶原蛋白原纤维，并迫使它们进行特殊的布置，以使角膜透明度允许角膜透明度。硫酸盐水平以前尚未直接在角膜中测量，因为这很难做到。我们将带来天体物理光谱专业知识，通常用于太空研究，以量化角膜发展的硫酸盐变化。这将教会我们如何硫化分子控制胶原蛋白的布置。毕竟，这项研究将教会我们在开发过程中以及在实验室中设计的角膜如何组装自身，以及角膜为何透明。我们还将开发其他科学家可以从中受益的生物物理学研究中的新技术。

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）

The corneal endothelium in development, disease and surgery

角膜内皮的发育、疾病和手术

DOI：
发表时间：
2013
期刊：
影响因子：
0
作者：
Jones Frances E.
通讯作者：
Jones Frances E.

A comparison of glycosaminoglycan distributions, keratan sulphate sulphation patterns and collagen fibril architecture from central to peripheral regions of the bovine cornea.

DOI：
10.1016/j.matbio.2014.06.004
发表时间：
2014-09
期刊：
MATRIX BIOLOGY
影响因子：
6.9
作者：
Ho, Leona T. Y.;Harris, Anthony M.;Tanioka, Hidetoshi;Yagi, Naoto;Kinoshita, Shigeru;Caterson, Bruce;Quantock, Andrew J.;Young, Robert D.;Meek, Keith M.
通讯作者：
Meek, Keith M.

Differential relative sulfation of Keratan sulfate glycosaminoglycan in the chick cornea during embryonic development.

胚胎发育过程中鸡角膜中硫酸角质素糖胺聚糖的相对硫酸化差异。