生物谷报道:2007年3月22日—由德克萨斯大学Galveston医学分校及从该校剥离出的Neurobiotex公司的科学家组成的一个国际研究小组发现，眼中高浓度的锌沉积是老年黄斑变性的一个标志。这项研究的资深作者，德州大学医学分校的眼科专家Erik van Kuijk声称，本月在《实验眼科研究》杂志上发表的这项发现，将加深人们对老年黄斑变性的理解，并有助于开发有效的治疗方法。
老年黄斑变性这种疾病的一个早期标志是在眼内形成一些微小的斑状物，被称作玻璃膜疣（drusen）。玻璃膜疣被认为是该疾病的一种触发原因，这种斑状的玻璃膜疣究竟因何形成，如何作用，至今仍然没有完全了解。
在此之前人们已经知道锌能促使阿尔茨海默症患者形成脑斑，因此，van Kuijk及其同事根据逻辑推理，锌也许也能促使眼中斑状的玻璃状疣形成。随即他们对这一设想进行了检验。Frederickson提出，可把老年黄斑变性当作“眼睛的阿尔茨海默症”，因为这两种异常都涉及错误折叠的淀粉样蛋白与金属（象锌和铜）聚集，形成被称作斑的微小的团块。
研究人员们检查了从蒙大拿眼睛库从死去的老年黄斑变性患者处得来的眼睛，这些眼睛在视网膜色素上皮下有一些较大的沉积。并将它们与类似年龄组的其它死者的眼睛作了比较，这些眼睛没有已知眼睛疾病且在黄斑上没有沉积。实验中他们使用了由Galveston市Neurobiotex公司的Christopher教授开发的一种叫ZP-1的试剂。ZP-1是一种锌感应分子，在与锌结合时会发光，但其只与游离的或结合松散的锌结合，这种锌对造成该疾病特别关键。
“van Kuijk博士及其同事的先驱性工作对我们理解老年黄斑变性是一项很重要的进展。”德州大学医学分校新设立的黄斑变性研究中心主任Michael Boulton说道。 “以锌为目标来使玻璃状疣逆转或停止生长，这种可能性很重要。因为这样做有可能能够在视网膜细胞出现不可逆转的损害之前，及早制止老年黄斑变性。”
原文出处:
Scientists Discover Zinc Link to a Leading Cause of Blindness
03/22/07 -- An international research team including scientists at the University of Texas Medical Branch at Galveston (UTM and the Galveston-based spinoff Neurobiotex, Inc. has found high levels of zinc in deposits in the eye that are an indication of age-related macular degeneration (AMD) ? the leading cause of blindness in the elderly in the developed world.
The finding, published this month in the journal Experimental Eye Research, contributes to a better understanding of AMD and could facilitate the development of effective treatments, said UTMB ophthalmologist Erik van Kuijk, senior author of the study.
AMD is a form of macular disease that affects the eye's central retina and afflicts millions of people (30 percent of them over 75 years old) in the United States alone. It is associated with defects of retinal pigment epithelial cells (RPE), the failure of which leads to progressive loss of vision. Despite the potentially devastating impact on patients' quality of life, no successful therapy to stop or reverse the progression of AMD is available in the majority of cases.
An early sign and a presumed trigger of the eye disease is the formation of microscopic plaques, called "drusen," in the eye. Exactly what these plaque-like drusen do and why they form is not yet fully understood, the researchers noted. "We have discovered that the drusen in the eyes of those with AMD have very high levels of zinc," said van Kuijk, associate professor in the UTMB Department of Ophthalmology and Visual Sciences.
Zinc previously had been shown to contribute to the formation of brain plaques in patients with Alzheimer's disease, so van Kuijk said it was logical for him and his colleagues to test the idea that zinc might also contribute to the formation of the plaque-like drusen in the eye. He said they did so using a reagent called ZP-1 that was developed by Dr. Christopher Frederickson at Neurobiotex, Inc. in Galveston. Frederickson suggested that AMD can be considered "the Alzheimer's disease of the eye," in that both disorders involve the aggregation of misfolded amyloid proteins and metals like zinc and copper into microscopic clumps called plaques.
"What is particularly important is that within the zinc we found a small pool ? about 5 to 10 percent ? of what is known as 'free' or 'loosely bound' zinc," van Kuijk explained. "Generally, zinc is essential to keeping a molecule's shape, but mobilized zinc can cause lots of problems. However, since it is a small proportion of the overall zinc pool, it's straightforward to target it. That's what researchers are beginning to do with Alzheimer's disease by developing methodologies and drugs that can capture this mobilized zinc and see if doing that slows down the degenerative process. This study shows that we could now potentially take a similar route for AMD treatment."
The researchers looked at eyes procured by the Montana Eye Bank from deceased patients with AMD that contained several large sub-RPE deposits and compared them to postmortem eyes from a similar age group that had no known eye disease and no deposits in the macula. They analyzed these using zinc-sensing molecules like ZP-1, which glow when they bind with zinc. These "glowing molecules" bind only to the free or loosely bound zinc, which is particularly crucial in causing disease.
Although total blindness almost never occurs as a result of AMD, a central portion of vision is lost, van Kuijk noted. This means that the condition can cause serious problems with reading, recognizing people, seeing small objects and driving. The disease is more common in women than in men. Common risk factors are family history and smoking. There are two forms of AMD ? dry and wet. Dry AMD means visual cells simply stop functioning, whereas wet AMD is linked to new vessel growth and is the more aggressive form of the disease. Currently there is no treatment for dry AMD, but there has been considerable progress in treating wet AMD, including use of new drugs like Avastin and Lucentis that stop new vessel growth. However, these are only suitable for patients with advanced disease, their effects are often temporary, and they carry the risk of adverse reactions.
"The pioneering work by Dr. van Kuijk and his colleagues is an important development in our understanding of AMD" said Dr Michael Boulton, director of the new Macular Degeneration Center at UTMB. "The possibility of targeting zinc to stop or reverse drusen growth is important because doing so has the potential to arrest the progression of AMD early, before irreversible damage to the retinal cells occurs."
"A treatment for AMD is desperately needed as the disease affects up to 7 million Americans," Boulton continued. "This equates to 2,000 AMD sufferers here on Galveston Island."
Source: University of Texas Medical Branch at Galveston
http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=27300019
背景知识：
黄斑变性是发达国家中老年人失明的主要原因，仅在美国就有成千上万（在75岁以上的人中有30%的人患病）的人受到这种疾病的折磨。老年黄斑变性是黄斑疾病，它与视网膜色素上皮细胞的缺陷有关，视网膜色素上皮细胞的淍亡可导致进行性失明。
尽管老年黄斑变性从来不会导致彻底失明的发生，但会使视野的中间部分丧失。这意味着这种情况会在阅读、辩人、看小物品及驾驶时导致严重的问题，这对患者的生活质量是一种沉重的打击。这种疾病在女性中比在男性中常见。 通常的危险因素是家族史和吸烟。老年黄斑变性有两种形式，干性型和湿性型。 干性型的老年黄斑变性意味着视觉细胞干脆不再起作用，而湿性型老年黄斑变性则与新血管生长有关联。 目前对干性型的老年黄斑变性无法治疗，但在治疗湿性型的老年黄斑变性方面则取得了相当的进展，包括使用象阿瓦斯丁和Lucentis等能够使血管生长停止的药物。 但是，这些治疗方法都只适用于患病晚期的患者，而且它们的效果通常是暂时的，并且还有不良反应的危险。
