Cataract Study--NASA Dynamic Light Scattering Device

白内障研究--NASA动态光散射装置

• 批准号: 7141735
• 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/7141735
• 关键词: bioengineering /biomedical engineering; biomedical equipment development; cataract; chemical aggregate; clinical biomedical equipment; early diagnosis; human subject; lens proteins; light scattering; miniature biomedical equipment; molecular pathology; molecular shape; molecular weight; protein structure

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. These in vivo, non invasive lens aging and cataract studies were not possible because we had no way to detect and quantify these early lens and cataract changes in the molecular level. This new easy to use device offers a new, sensitive and precise method to study conditions and medications that can either cause cataract or prevent cataract. Preliminary analysis of the data shows good correlation between DLS and Clinical Lens Grading data, suggesting that the DLS method can determine the severity of clouding of the lens (cataract) objectively without the need of an ophthalmological exam, making it also useful in field studies. We are continuing to study how the resulting complex data represents molecular lens changes. If successful then, the development of this technique will help us conduct future clinical cataract studies of all sorts, with great sensitivity and accuracy, as well as for shorter durations and at lower expense. The resulting information will help us to better understand the underlying causes of cataracts and help us develop and test new treatments to delay, reverse or prevent cataract formation.

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，这将有助于我们找到治疗白内障的方法。关于白内障病因的一种理论是，某些因素如阳光或缺乏保护性抗氧化维生素，可能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（动态光散射装置或DLS）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。在白内障动物模型上使用新的DLS装置，我们发现了白内障发展时这种透镜蛋白聚集的证据。初步研究表明，它在检测白内障发生的最早变化方面具有潜力，在这个阶段，抗白内障治疗理论上最有效地逆转、延迟或预防白内障。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2阶段，研究由于老化（年龄相关变化）而导致的人体透镜体内的临床变化，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，随着正常老化，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。在白内障形成过程中，我们观察到低分子量蛋白质的丢失和高分子量蛋白质的急剧增加，使得所有蛋白质都可能最终形成一个大分子量峰，特别是在核白内障中。在某些皮质性和后囊下白内障中，即使核保持清晰且似乎未受影响，透镜核也有明显的分子变化。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。 这些体内、非侵入性透镜老化和白内障研究是不可能的，因为我们没有办法在分子水平上检测和量化这些早期透镜和白内障变化。这种新的易于使用的设备提供了一种新的，灵敏和精确的方法来研究可能导致白内障或预防白内障的条件和药物。数据的初步分析显示，DLS和临床透镜分级数据之间具有良好的相关性，表明DLS方法可以客观地确定透镜混浊（白内障）的严重程度，而无需眼科检查，使其在现场研究中也很有用。我们正在继续研究所得到的复杂数据如何代表分子透镜的变化。如果成功的话，这项技术的发展将有助于我们进行未来的各种临床白内障研究，具有很高的灵敏度和准确性，以及更短的持续时间和更低的费用。由此产生的信息将帮助我们更好地了解白内障的根本原因，并帮助我们开发和测试新的治疗方法，以延迟，逆转或预防白内障的形成。