Towards a functional understanding of proteoglycan-collagen associations in the cornea by 3-dimensional electron microscopy of gene-targeted mutants

角膜是眼睛前部透明的部分。它对正常的视力至关重要，因为它让光线进入并将其聚焦在眼睛后部的视网膜上。从而形成清晰的图像，我们可以正确地看到。角膜是一种特殊的组织，因为它是透明的，在这方面，它不像身体中的其他相关组织--例如连接我们骨骼和肌肉的肌腱或巩膜（眼睛的白色）--它们是由类似的成分组成的。科学家们认为，角膜是透明的，因为形成角膜的大部分蛋白质称为胶原蛋白，主要是长而细的绳状结构，称为原纤维。此外，这些胶原纤维形成了一个非常明确的安排，让光通过。如果这种排列被破坏，角膜就会失去透明度并变得浑浊。因此，视力严重受损。有趣的是，科学家们怀疑角膜中被称为蛋白聚糖的分子影响了胶原纤维，并迫使它们采取特殊的排列方式，使角膜透明。以前的研究已经使用经过基因修饰的小鼠角膜研究了胶原蛋白和蛋白聚糖之间的结构关系，使它们不具有某些类型的蛋白聚糖。这允许理解不同蛋白聚糖亚型的结构。但是，到目前为止，只能通过在电子显微镜上检查角膜的非常薄的切片来研究胶原蛋白和蛋白聚糖的二维结构，因此我们可以得到的理解是有限的。然而，现在我们能够使用电子显微镜的新改进来产生胶原蛋白和蛋白聚糖的图像，使我们能够看到它们的三维结构。因此，该项目将以前所未有的细节发现角膜中胶原蛋白和蛋白聚糖之间的联系，并将帮助我们了解角膜的结构和透明度是如何保持的。

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 -- which 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. Interestingly, scientists suspect that molecules called proteoglycans in the cornea influence the collagen fibrils and force them to take up the special arrangement that allows corneal transparency. Previous investigations have studied the structural relationship between collagen and proteoglycans using the corneas of mice that have been genetically modified so that they don't possess certain types of proteoglycan. This allows the structure of different proteoglycan sub-types to be understood. But, up to now it has only been possible to study the collagen and proteoglycan structures in 2 dimensions by examining very thin sections of cornea on an electron microscope, so the understanding that we can get is limited. Now, however, we are able to use a new modification of electron microscopy to produce images of the collagen and proteoglycans that allows us to see their structures in 3 dimensions. This project will thus discover the links between collagen and proteoglycans in the cornea in a detail not seen previously, and will help us to understand how the structure and transparency of the cornea is maintained.