Cataract Study--NASA Dynamic Light Scattering Device

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。尽管手术在美国容易获得且安全进行，但在亚洲、非洲、中东和南美洲等世界许多不发达地区，手术并不容易获得，也不安全进行。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找出可能导致白内障的人类晶状体发生了什么，这将帮助我们找到治疗白内障的方法。关于白内障病因的一种理论是，某些因素，如阳光或缺乏保护性抗氧化剂维生素，可能会导致晶状体内的蛋白质聚集形成不透明的高分子质量“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，包括发生在晶状体核中的晶状体相互作用。在白内障动物模型上使用新的DLS设备，我们发现了随着白内障的发展，晶状体蛋白聚集的证据。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，在这一阶段，理论上抗白内障治疗在逆转、延迟或预防白内障方面最有效。NASA使用较低能量的激光开发了该设备的一个新的微型版本，并在NEI提供了进一步的开发和临床测试。我们成功地将DLS装置安装在角膜镜上，角膜镜上有一个三维瞄准系统，以提高重复性。 我们最近在正常人志愿者身上进行了一项初步研究(第一阶段)，以评估该仪器用于量化晶状体变化的有用性和重复性，并发现良好的重复性。我们还确定可以使用的最有用的参数是由粒度分布得出的平均粒度。 我们现在处于该项目的第二阶段，研究由于年龄增长而导致的体内人类晶状体的临床变化(与年龄相关的变化)，以及在三种典型类型的白内障(核型、皮质型和PSC型)中发现的分子变化。我们发现，在正常老化的情况下，低分子量和高分子量晶状体蛋白都会向增加更高分子量的方向转变。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，因此所有的蛋白质都可能最终形成一个大分子量峰，特别是在核性白内障中。在一些皮质和后囊下白内障中，即使在核保持透明和似乎不受影响的情况下，晶状体核也有明显的分子变化。这些数据将有助于描述人类晶状体中与正常衰老相关的分子变化以及与白内障形成相关的分子变化。 这些活体、非侵入性的晶状体老化和白内障研究是不可能的，因为我们无法在分子水平上检测和量化这些早期晶状体和白内障的变化。这一新的易于使用的设备为研究可能导致白内障或预防白内障的条件和药物提供了一种新的、灵敏和精确的方法。对数据的初步分析表明，DLS方法与临床晶状体分级数据具有良好的相关性，表明DLS方法可以在不需要眼科检查的情况下客观地确定晶状体混浊(白内障)的严重程度，使其在现场研究中也很有用。我们正在继续研究由此产生的复杂数据如何代表分子透镜的变化。如果成功，这项技术的发展将帮助我们进行未来各种类型的临床白内障研究，具有极高的敏感性和准确性，以及更短的持续时间和更低的费用。由此得到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来延迟、逆转或预防白内障的形成。

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.