Normal-Diseased Corneas NASA-NEI CLINICAL DLS DEVICE

正常患病角膜 NASA-NEI 临床 DLS 设备

• 批准号: 7141750
• 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/7141750
• 关键词: aging; biomedical equipment development; blindness; cataract; clinical biomedical equipment; cornea; cornea disorder; cornea opacity; diabetic cataract; diagnosis design /evaluation; diagnostic tests; early diagnosis; eye disorder diagnosis; eye infections; eye surgery; human subject; inflammation; light scattering; molecular pathology; noninvasive diagnosis; patient oriented research; postoperative state; trauma; wound healing

The transparent cornea, located in the front of the eye, acts not only as a refracting medium to focus light on the retina and help us see, but also serves as the main barrier and structure in the front of the eye. Serious disease of the cornea leads to opacification and blindness. Corneal diseases and injuries are the leading reason for visits to eye care clinics in the U.S. today. These diseases are also some of the most painful eye disorders. Two important areas for research on the cornea are: 1) to explore and understand the molecular basis of corneal transparency, and 2) to analyse the molecular nature of corneal wound healing and inflammation. We developed a new clinical device to understand molecular changes that occur in the lens, the NASA-NEI Dynamic Light Scattering (DLS) device, which could also be useful in the Cornea. Laboratory studies have shown its potential in the detection of the earliest changes occuring in cataracts. Clinical studies on the lens have also shown good test-retest reproducibility, sensitivity to pick up small changes, and safety of the non-invasive, in vivo DLS clinical cataract system. We initially conducted laboratory studies in animals to determine if the DLS device is also useful to study the cornea. We found that it can detect molecular differences in various layers/compartments of the cornea in the normal state. In addition, we found that after corneal injury such as after laser photorefractive surgery, chemical injury and scraping, the DLS could detect changes which are not apparent or detectable using optical devices such as the slit lamp biomicroscope. This suggest that the DLS may be useful as a non-invasive, in vivo device to study the cornea in the normal state as well as in diseased states and to understand the molecular basis of corneal transparency. In this pilot project, we studied normal, post surgical and diseased corneas in volunteers. In preliminary testing, it was determined that the DLS clinical cataract device is not properly suited for the cornea. This is because of the difference in thickness between the cornea and the lens (0.5 mm in the human cornea versus 3-4 mmm in the human lens), so that the angle of entry of the Helium Neon Light beam versus the angle of the APD light detector is not correct. Hence we developed a new NASA-NEI DLS device for the cornea. After a number of stages of DLS device modifications done by our NASA collaborators (engineers and physicists) based on tests on our volunteers, we have now obtained good repeatable corneal measurements. We found the following: First, the DLS device detected basic differences in protein composition between cornea, lens and vitreous, and showed distinct signals from corneal glycoproteins and collagen. Second, in comparing normal and diseased corneas, there were distinct differences in protein composition between normal, diabetic and post surgical (LASIK) corneas. In normal corneas, there are 2 protein groups, one in the 1000 nm diameter size and another in the 5000 nm size. In post LASIK corneas, there is a peak in the 1000 nm size but the second peak (larger molecular weight) is in the 8000 nm size area. In diabetics, the lower molecular weight group ranges from about 200 to 1000 nm size (wider spread) and the large molecular weight proteins are spread from 2000 to 25,000 nm size (much wider spread). These were all performed easily and safely, in vivo (clinically), objectively and non invasively. These findings suggest that this new DLS clinical corneal device may be useful in detecting and studying corneal abnormalities in the molecular level. In particular, it may be useful in detecting corneal changes after LASIK surgery as well as in diabetes and other disorders.

透明的角膜位于眼睛前部，不仅作为折射介质将光线聚焦在视网膜上并帮助我们看东西，而且还作为眼睛前部的主要屏障和结构。严重的角膜疾病会导致混浊和失明。角膜疾病和损伤是当今美国眼科诊所就诊的主要原因。这些疾病也是一些最痛苦的眼部疾病。角膜研究的两个重要领域是：1）探索和理解角膜透明度的分子基础，2）分析角膜伤口愈合和炎症的分子本质。 我们开发了一种新的临床设备来了解透镜中发生的分子变化，即NASA-NEI动态光散射（DLS）设备，该设备也可用于角膜。实验室研究表明，它在检测白内障发生的最早变化方面具有潜力。对透镜的临床研究也显示了良好的重复测试再现性、拾取微小变化的灵敏度以及非侵入性体内DLS临床白内障系统的安全性。 我们最初在动物身上进行了实验室研究，以确定DLS设备是否也可用于研究角膜。我们发现它可以检测正常状态下角膜各层/隔室中的分子差异。此外，我们发现，角膜损伤后，如激光屈光手术，化学损伤和刮伤后，DLS可以检测到的变化是不明显的或使用光学设备，如裂隙灯生物显微镜检测。这表明，DLS可能是有用的，作为一种非侵入性的，在体内的设备，以研究角膜在正常状态以及在患病状态，并了解角膜透明度的分子基础。 在这个试点项目中，我们研究了志愿者的正常，手术后和患病角膜。在初步测试中，确定DLS临床白内障器械不适合角膜。这是因为角膜和透镜之间的厚度差异（人角膜为0.5 mm，人透镜为3-4 mm），因此氦氖光束的入射角与APD光检测器的角度不正确。 因此，我们开发了一种新的NASA-NEI角膜DLS设备。在我们的NASA合作者（工程师和物理学家）根据对志愿者的测试进行了多个阶段的DLS设备修改后，我们现在已经获得了良好的可重复角膜测量结果。我们发现以下内容：首先，DLS设备检测到角膜、透镜和玻璃体之间蛋白质组成的基本差异，并显示出来自角膜糖蛋白和胶原蛋白的不同信号。其次，在比较正常和患病角膜时，正常、糖尿病和手术后（LASIK）角膜之间的蛋白质组成存在明显差异。在正常角膜中，有2个蛋白质组，一个直径为1000 nm，另一个直径为5000 nm。在LASIK后角膜中，在1000 nm尺寸中存在峰，但第二峰（较大分子量）在8000 nm尺寸区域中。在糖尿病患者中，较低分子量组的范围为约200至1000 nm大小（更宽的范围），而大分子量蛋白质的范围为2000至25，000 nm大小（更宽的范围）。这些都是容易和安全地进行，在体内（临床），客观和非侵入性。这些发现表明，这种新的DLS临床角膜装置可能是有用的检测和研究角膜异常的分子水平。特别是，它可以用于检测LASIK手术后的角膜变化以及糖尿病和其他疾病。