Cataract And Lens Aging Study With The Dynamic Light Sca

使用动态光扫描仪进行白内障和晶状体老化研究

• 批准号: 6826923
• 负责人: Manuel B Datiles
• 金额: --
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6826923
• 关键词: aging; blindness; cataract; chemical aggregate; clinical research; cornea; diagnosis design /evaluation; early diagnosis; eye disorder diagnosis; human subject; lens; lens proteins; nephelometry; patient oriented research

Cataracts are the foremost cause of blindness in the world and currently can be treated only by surgical removal. Surgery, although easily available and safely performed in the U.S., is not easily available nor safely performed in many undeveloped regions in the world like Asia, Africa, the Middle East and South America. Hence we are studying ways to treat cataracts non-surgically, and a new device promises to help us find out what happens to the human lens that may cause cataracts, which will then help us find a cure for cataracts.One theory on the cause of cataracts is that some factors such as sunlight or lack of protective anti-oxidant vitamins may cause the proteins inside the lens to aggregate to form opaque high molecular weight "aggregates". Recently, a device has been created to determine molecular interactions, including lens crystalline interactions that occur in the nucleus of the lens, called Dynamic Light Scattering Device (DLS). Using the new DLS device on animal models of cataract, we have found evidence of this aggregation of proteins as a cataract appears.Preliminary studies have shown its potential in the detection of the earliest changes occurring in cataract, at the stage where anticataract treatment would theoretically be most effective in reversing, delaying or preventing cataracts. A new miniaturized version of this device has been developed by NASA using lower energy lasers and offered for further development and clinical testing at the NEI. We mounted the DLS device successfully on the Keratoscope, which had a 3-D aiming system to enhance repeatability. We recently conducted a pilot study on normal human volunteers (Phase 1) to evaluate the usefulness and reproducibility of this instrument for quantitating lens changes, and found good reproducibility. We also determined that the most useful parameter to use is mean particle size derived from particle size distribution. We are now in Phase 2 of this project, studying changes in the lens due to aging (age related changes), as well as molecular changes found in the three representative types of cataracts (nuclear, cortical and PSC). We found that with aging, there is a shift of both low and high molecular weight lens proteins toward increasing higher molecular weights, and dramatic shifts at the start of cataract formation. There is also loss of low molecular weight proteins, and more so when a cataract forms, especially in nuclear cararact. In cortical and posterior subcapsular cataracts, there are marked molecular changes in the lens nucleus even when the nucleus remains clear and does not seem to be affected. These data will help characterize molecular changes in the human lens associated with normal aging as well as those associated with cataract formation. We will soon move into Phase 3 of the study involving use of the DLS device to detect and follow the earliest changes in cataract formation over time (longitudinal study). With this information, we hope to better understand the underlying causes of cataracts and, in the future, develop medications to delay or prevent cataract formation. Finally, we recently explored the use of the NASA-NEI DLS device to study the cornea. Bovine eyes were studied in the normal state as well as treated with chemicals, scraped using cotton swabs with or withour alcohol, and underwent radial keratotomy and photo-refractive surgery.Dynamic and Staticight Scattering techniques were used to study the molecular characteristics opf different layers of the normal cornea as well as after injury. We found that this technique was indeed useful in characterizing different layers of the normal cornea as well as revealed molecular metabolic changes not visible using optical devices such as the slit lamp biomicroscope and therefore holds promise as a tool to study the basis of corneal transparency as well as molecular changes after croneal injury and surgery such as LASIK surgery and Corneal transplantation. Hence we are now moving into Phase 1/Pilot clinical studies using a modified clinical DLS device to study normal and abnormal human corneas in vivo.

白内障是世界上最主要的致盲原因，目前只能通过手术切除来治疗。手术，虽然在美国很容易获得和安全地进行，在世界上许多不发达地区，如亚洲、非洲、中东和南美洲，因此，我们正在研究非手术治疗白内障的方法，一种新的设备有望帮助我们找到可能导致白内障的人类透镜发生的变化，这将帮助我们找到治疗白内障的方法。关于白内障的原因，有一种理论认为，一些因素，如阳光或缺乏保护性的抗氧化维生素，可能会导致透镜内的蛋白质聚集，形成不透明的高分子量“聚集体”。最近，已经创建了一种装置来确定分子相互作用，包括在透镜的核中发生的透镜晶体相互作用，称为动态光散射装置（DLS）。在白内障动物模型上使用新的DLS设备，我们发现了白内障出现时蛋白质聚集的证据。初步研究表明，在抗白内障治疗理论上最有效逆转、延迟或预防白内障的阶段，它在检测白内障发生的最早变化方面具有潜力。NASA使用低能量激光器开发了这种设备的新小型化版本，并在NEI进行了进一步的开发和临床测试。我们成功地将DLS设备安装在角膜镜上，角膜镜具有3-D瞄准系统以提高可重复性。我们最近对正常人类志愿者进行了一项初步研究（第1阶段），以评估该仪器用于定量透镜变化的有用性和重现性，并发现良好的重现性。我们还确定了最有用的参数是来自粒度分布的平均粒度。我们现在正处于该项目的第二阶段，研究由于衰老引起的透镜的变化（年龄相关变化），以及在三种代表性类型的白内障（核性、皮质性和PSC）中发现的分子变化。我们发现，随着年龄的增长，低分子量和高分子量的透镜蛋白质都向更高分子量的方向转移，并且在白内障形成开始时发生了显著的变化。也有低分子量蛋白质的损失，当白内障形成时更是如此，特别是在核性白内障中。在皮质性和后囊下白内障中，透镜核有明显的分子变化，即使核保持清晰，似乎没有受到影响。这些数据将有助于表征与正常老化以及与白内障形成相关的人类透镜的分子变化。我们将很快进入研究的第3阶段，包括使用DLS设备检测和跟踪白内障形成随时间的最早变化（纵向研究）。有了这些信息，我们希望更好地了解白内障的根本原因，并在未来开发药物来延迟或预防白内障的形成。 最后，我们最近探索了使用NASA-NEI DLS设备来研究角膜。本文对牛眼在正常状态下、化学药物处理后、用含酒精或不含酒精的棉签刮取、放射状角膜切开术和屈光手术后的角膜进行了研究，用动态和静态散射技术研究了正常和损伤后角膜各层的分子特征。我们发现，这项技术确实是有用的，在表征不同层的正常角膜，以及揭示分子代谢的变化不可见的使用光学设备，如裂隙灯生物显微镜，因此持有承诺作为一种工具，研究角膜透明度的基础，以及分子变化后croneal损伤和手术，如LASIK手术和角膜移植。因此，我们现在正在进入1期/试点临床研究，使用改良的临床DLS装置在体内研究正常和异常的人角膜。