HYALURONIC ACID IN NORMAL, AGED, AND DISEASED VITREOUS

玻璃体是一种凝胶状结缔组织，有两大分子 成分、胶原蛋白和透明质酸。胶原蛋白分子是 对凝胶结构负责，而透明质酸被认为是 保持结构的完整性。在衰老或疾病中，透明质酸 酸经常被降解，而且降解通常是由活性自由基引起的 或酶促或非酶促生成的自由基离子物种。在……里面 在这个过程中，玻璃体的凝胶结构往往会丢失，并在 透明质酸的结构(构象)及其相互作用性质 都有可能发生。 我们的初步研究表明，当透明质酸被降解时， 它的构象不同于正常的(分子量减少)。在……里面 为了了解透明质酸在玻璃体和玻璃体内的作用 分子的结构-功能关系，我们计划对其进行详细研究 (1)不同分子的透明质酸的构象 重量，(2)透明质酸在体内降解的机制 衰老和疾病状态，(3)透明质酸变化的性质 它遭受退化，(4)相互作用是否有任何变化 胶原蛋白和降解的透明质酸之间的性质，以及(5)可能 青年、老年人和疾病患者透明质酸的结构变化 玻璃体，如果有的话。低分子量透明质酸的制备 (寡糖)，我们将使用透明质酸酶，并研究其作用机理 我们将使用酶和非酶产生的降解 自由基和自由基离子。光谱技术，如圆形 将使用二色性和荧光(使用荧光探针)来研究 透明质酸的分子性质。其他技术，例如 粘度、电子显微镜和光散射测量将被 适用时使用。这项建议的长期目标是 确定结构紊乱的生化和生物物理基础 在老化过程中和在疾病状态下的玻璃体。玻璃体 异常是老年人和眼科疾病的常见现象。 如近视、视网膜色素变性和糖尿病视网膜病变。 凝胶液化或收缩、膜形成和视网膜 很多情况下会发生剥离。这个项目预计将产生 这些信息将提供一些对这些问题的原因的洞察 异常现象。

The vitreous body is a gel-like connective tissue two major macromolecular components, collagen and hyaluronic acid. The collagen molecule is responsible for the gel structure, and hyaluronic acid is believed to maintain the integrity of the structure. In aging or disease, hyaluronic acid is often degraded, and degradation is often caused by active radical or radical ion species generated enzymatically or non-enzymatically. In this process, gel structure of the vitreous is often lost, and changes in the structure (conformation) and interaction properties of hyaluronic acid are likely to occur. Our preliminary studies indicated that when hyaluronic acid is degraded, its conformation is defferent from normal (decreased molecular weight). In order to understand the role of hyaluronic acid in the vitreous and the structure-function relationship of the molecule, we plan to study in detail (1) the conformational aspects of hyaluronic acid of different molecular weights, (2) the mechanism by which hyaluronic acid is degraaded in the aged and diseased state, (3) the nature of changes of hyaluronic acid when it suffers degradation, (4) whether there is any change in the interaction properties between collagen and degraded hyaluronic acid, and (5) possible structural changes of hyaluronic acid in young, old, and diseased human vitreous, as available. To obtain low-molecular-weight hyaluronic acid (oligosaccharides), we will use hyaluronidase, and to study the mechanism of degradation we will use enzymatically and nonenzymatically generated radicals and radical ions. Spectroscopic techniques such as circular dichroism and fluorescence (using fluorescent probe) will be used to study the molecular properties of hyaluronic acid. Other techniques, such as viscosity, electron microscopy, and light scattering measurements will be used when applicable. The long-term objective of this proposal is to determine the biochemical and biophysical basis for the structural disorder of the vitreous in the aging process and in diseased states. Vitreous abnormalities are common phenomena in aging individuals and in eye diseases such as myopia, retinitis pigmentosa, and diabetic retinopathy. Liquefaction or shrinkage of the gel, membrane formation, and retinal detachment occur in many cases. This project is expected to yield information that will provide some insight into the cause of those abnormalities.