Cataract And Lens Aging Study With The Dynamic Light Sca

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。关于白内障原因的一种理论是，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，人们发明了一种设备来确定分子相互作用，包括发生在晶状体核中的晶状体相互作用，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，我们发现了当白内障出现时蛋白质聚集的证据。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，在理论上，抗白内障治疗在逆转、延迟或预防白内障方面是最有效的阶段。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。我们现在处于这个项目的第二阶段，研究晶状体因年龄而发生的变化(与年龄相关的变化)，以及在三种典型类型的白内障(核性、皮质型和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晶状体蛋白都会朝着增加更高分子量的方向转变，在白内障形成的开始阶段会发生戏剧性的转变。低分子量蛋白质也会丢失，当白内障形成时更是如此，特别是在核性白内障中。在皮质和后囊下白内障中，即使在晶状体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。我们将很快进入研究的第三阶段，包括使用DLS设备来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潜在原因，并在未来开发延缓或预防白内障形成的药物。 最后，我们最近探索了使用NASA-NEI DLS设备来研究角膜。研究了牛眼在正常状态下和化学处理后，用棉签和酒精擦拭，并进行了放射状角膜切开术和光屈光手术，用动态和静态散射技术研究了正常角膜和损伤后不同层次的分子特征。我们发现，这项技术确实有助于描述正常角膜的不同层面，并揭示了使用裂隙灯生物显微镜等光学设备无法看到的分子代谢变化，因此有望成为研究角膜透明的基础以及角膜损伤和手术(如LASIK手术和角膜移植)后的分子变化的工具。因此，我们现在正在进入第一阶段/试点临床研究，使用改进的临床DLS设备在活体内研究正常和异常的人类角膜。

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.