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，一种被称为动态光散射装置（DLS）的装置被发明出来，用于确定分子相互作用，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设备，我们发现了白内障出现时蛋白质聚集的证据。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。我们最近对正常的人类志愿者进行了一项试点研究（第一阶段），以评估该仪器用于定量晶状体变化的有效性和可重复性，并发现了良好的可重复性。我们还确定了最有用的参数是由粒度分布得出的平均粒度。我们现在正在这个项目的第二阶段，研究晶状体因衰老而发生的变化（与年龄相关的变化），以及在三种典型类型的白内障（核性、皮质性和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的晶状体蛋白都朝着更高分子量的方向转变，并且在白内障形成开始时发生了戏剧性的变化。低分子量蛋白质也会丢失，尤其是在白内障形成时，尤其是在核性白内障中。在皮质性和后囊膜下白内障中，晶状体核有明显的分子变化，即使晶状体核仍然清晰，似乎没有受到影响。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的早期变化（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，并在未来开发药物来延缓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 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.