PHYSICAL AND CHEMICAL BASIS OF LENS OPACITY

晶状体混浊的物理和化学基础

• 批准号: 3259980
• 负责人: GEORGE B BENEDEK
• 金额: $ 16.59万
• 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 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3259980
• 关键词: biomedical equipment resource; body fluid viscosity; cataract; cellular pathology; chemical aggregate; clinical biomedical equipment; corneal stroma; crosslink; cytoplasm; disease /disorder model; early diagnosis; eye disorder diagnosis; gel electrophoresis; lens; lens proteins; light scattering; noninvasive diagnosis; nuclear magnetic resonance spectroscopy; ocular hypotensive; phase change; spectrometry

Our long term objectives are to determine the biophysical basis of cataract formation, and to identify chemical means for the inhibition or reversal of cataract both in mammalian systems and in humans. To achieve these objectives we present briefly below the specific aims of the proposed research. 1. To determine the microscopic structure and composition of the molecular aggregates responsible for the scattering of light and opacification of the lens in cataract. 2. To identify reagents which can inhibit or reverse cataract formation. These reagents will first be evaluated for their effectiveness in suppressing phase separation cataract using concentrated solutions of purified lens crystallins, lens cytoplasmic homogenates, and then whole mammalian lenses in vitro. The reagents will also be tested for their effectiveness in suppressing cataracts produced by known cataractogenic agents such as oxidizing agents, high salt, calcium and sugars acting on the systems mentioned above. 3. To develop the method of quaielastic light scattering spectroscopy for clinical use in vivo, in order to detect non-invasively very early stages of cataract development. 4. To conduct initial tests of the ability of the instrument, which is mentioned in (3), to provide a new, non-invasive method for the quantitative characterization of the viscoelastic properties of the collagen fiber network in both normal corneal stroma and in corneas undergoing early pathological changes. 5. To use high resolution nuclear magnetic resonance measurements of chemical shifts and relaxation times to study: (a) Differences in composition and environment of amino acid side chains of individual purified lens protein fractions. (b) The degree of cross linking produced by cataract inhibiting reagents. (c) The relative proportions of protein-rich and protein-poor phase along the coezistence curve for protein phase separation.

我们的长期目标是确定白内障的生物物理基础 形成，并确定抑制或逆转的化学方法 在哺乳动物系统和人类中白内障。 实现这些 我们在提议的具体目的下方简要提出了目标 研究。 1。确定分子的显微镜结构和组成 负责光散射和不透明的聚集体 白内障中的镜头。 2。确定可以抑制或反向白内障形成的试剂。 这些试剂将首先评估其在 使用集中溶液抑制相位分离白内障 纯化的透镜结晶，透镜细胞质匀浆，然后全部 体外哺乳动物镜片。 试剂还将对其进行测试 抑制已知白内障产生的白内障的有效性 氧化剂，高盐，钙和作用于作用的糖的剂 上面提到的系统。 3。开发Quai弹性光散射光谱法的方法 在体内使用临床用途，以检测到非常早期的非侵入性 白内障发育。 4。进行仪器能力的初步测试，即 在（3）中提到的是为了提供一种新的非侵入性方法 定量表征的粘弹性特性 正常角膜基质和角膜中的胶原蛋白纤维网络 经历早期的病理变化。 5。使用高分辨率的核磁共振测量 化学移位和放松时间进行研究： （a）氨基酸侧链的组成和环境的差异 个体纯化的透镜蛋白分数。 （b）白内障抑制试剂产生的交叉连接程度。 （c）沿蛋白质富蛋白和贫困相的相对比例沿 蛋白相分离的同志曲线。