Cross Sectional Cataract Study With The NASA DLS Device

使用 NASA DLS 设备进行白内障横截面研究

• 批准号: 6968566
• 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/6968566
• 关键词: cataract; chemical aggregate; clinical biomedical equipment; human subject; lens proteins; light scattering; miniature biomedical equipment; molecular pathology; molecular weight

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 (the Dynamic Light Scattering device or DLS), has been created to determine molecular interactions, including lens crystalline interactions that occur in the nucleus of the lens. Using the new DLS device on animal models of cataract, we have found evidence of this lens protein aggregation as a cataract develops. 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 clinical changes in the human lens in vivo 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 normal aging, there is a shift of both low and high molecular weight lens proteins toward increasing higher molecular weights. During cataract formation, we have observed loss of low molecular weight proteins and dramatic increases in high molecular weight proteins, so that all the proteins could end up in a single large molecular weight peak, especially in nuclear cararact. In some 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. This information will help us to better understand the underlying causes of cataracts and, thereby help us develop and test (in Clinical Trials) medications to delay or prevent cataract formation. These in vivo, non invasive and sensitive normal lens aging and cataract studies were heretofore been impossible to conduct due to the absence of a method to detect and quantify these lens and cataract changes in the molecular level. The development of this safe clinical method and creation of this miniature and operator- and patient- friendly device is a first in this field of clinical cataract studies. It also offers a new more sensitive and precise method to conduct clinical (in vivo) lens studies and trials of conditions and medications that can either cause the development of cataract (toxic side effect) or prevent cataract development (beneficial effect) in man. If successful, the development of this technique will result in shorter and therefore less expensive longitudinal clinical lens and cataract studies.

白内障是世界上最主要的致盲原因，目前只能通过手术摘除来治疗。手术，虽然在美国容易获得和安全进行，但在世界上许多不发达地区，如亚洲，非洲，中东和南美洲，不易获得和安全进行。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发现可能导致白内障的人体晶状体发生了什么，这将帮助我们找到治疗白内障的方法。关于白内障原因的一种理论是，一些因素，如阳光照射或缺乏抗氧化维生素，可能导致晶状体内的蛋白质聚集，形成不透明的高分子量“聚集体”。最近，一种装置（动态光散射装置或DLS）已经被创造出来，以确定分子相互作用，包括发生在透镜核中的透镜晶体相互作用。在白内障动物模型上使用新的DLS装置，我们发现了这种晶状体蛋白在白内障发展过程中聚集的证据。初步研究表明，它在发现白内障发生的早期变化方面具有潜力，在这个阶段，抗白内障治疗理论上在逆转、延缓或预防白内障方面是最有效的。美国国家航空航天局（NASA）已经开发出一种新的小型化设备，使用较低能量的激光，并将在NEI进行进一步的开发和临床测试。我们成功地将DLS装置安装在具有三维瞄准系统的角膜镜上，以提高可重复性。