PHYSICAL AND CHEMICAL BASIS OF LENS OPACITY

晶状体混浊的物理和化学基础

• 批准号: 2159305
• 负责人: GEORGE B BENEDEK
• 金额: $ 33.38万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-05-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2159305
• 关键词: bioenergetics; cataract; cell osmotic pressure; chemical aggregate; covalent bond; crystallins; gel electrophoresis; human tissue; intraocular fluid; ionic strengths; lens; lens proteins; ligands; light scattering; molecular pathology; molecular weight; phase change; solutions; thermodynamics

Our overall objective is to identify the microscopic molecular factors which produce the scattering elements responsible for lens opacification. These elements are high molecular weight protein aggregates, and spatially segregated protein-rich and protein-poor domains produced by phase separation. To achieve this objective we propose the following lines of investigation. 1. To determine the location of phase boundaries and the equation of state for aqueous solutions of highly purified alpha, beta and gamma crystallins and mixtures of these for fixed physiological solution conditions. 2. To determine the effect of changes in solution conditions such as pH, and ionic strength and ion identity on the location of phase boundaries and the equation of state for the lens protein solutions above. 3. To evaluate the consequences of specific covalent modifications on the location of phase boundaries and the formation of high molecular weight aggregates in two- component and multi-component protein solutions. 4. To determine the effect of noncovalently binding ligands on the location of the phase boundaries in two-component and multi-component protein solutions. 5. To use the data on equation of state and phase boundaries obtained above to determine the factors which control osmotic water balance within the lens. 6. To obtain a quantitative theoretical understanding of the structure of the Gibbs free energy which can predict the equilibrium properties of the lens protein solutions studied.

我们的总体目标是确定微观分子因子 产生负责晶状体无情的散射元件。 这些元素是高分子量蛋白质聚集体，并在空间上 通过相产生的富含蛋白质的富含蛋白质和贫困域 分离。 为了实现这一目标，我们提出以下几行 调查。 1。确定相边界的位置和方程 高度纯化Alpha，beta和Gamma水溶液的状态 这些结晶蛋白和混合物用于固定生理溶液 状况。 2。确定解决方案条件变化的影响，例如 pH，离子强度和离子身份在相位的位置 边界和透镜蛋白溶液的状态方程 多于。 3。评估特定共价修改对 相边界的位置和高分子的形成 两种成分和多组分蛋白的重量聚集体 解决方案。 4。确定非共价结合配体对 相边界在两个组件和多组分中的位置 蛋白质溶液。 5。使用有关获得的状态和相边界方程的数据 以上以确定控制渗透水平衡的因素 在镜头内。 6。要获得对结构的定量理论理解 可以预测平衡特性的吉布斯自由能 研究的晶状体蛋白溶液。