Cross Sectional Cataract Study With The NASA DLS 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。这些信息将帮助我们更好地了解白内障的根本原因，从而帮助我们开发和测试(在临床试验中)延缓或预防白内障形成的药物。 到目前为止，由于缺乏在分子水平上检测和量化这些晶状体和白内障变化的方法，这些活体、非侵入性和敏感的正常晶状体老化和白内障研究是不可能进行的。这种安全的临床方法的开发和这种微型的、操作员和患者友好的设备的创造，在这一临床白内障研究领域是第一次。它还提供了一种新的更灵敏和精确的方法来进行临床(体内)晶状体研究和条件和药物的试验，这些条件和药物可能会导致人类白内障的发展(毒副作用)或预防白内障的发展(有益效果)。如果成功，这项技术的发展将导致更短的时间，因此更便宜的纵向临床晶状体和白内障研究。

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.