生物谷報(bào)道:2007年3月22日—由德克薩斯大學(xué)Galveston醫(yī)學(xué)分校及從該校剝離出的Neurobiotex公司的科學(xué)家組成的一個(gè)國際研究小組發(fā)現(xiàn),，眼中高濃度的鋅沉積是老年黃斑變性的一個(gè)標(biāo)志,。這項(xiàng)研究的資深作者，德州大學(xué)醫(yī)學(xué)分校的眼科專家Erik van Kuijk聲稱,，本月在《實(shí)驗(yàn)眼科研究》雜志上發(fā)表的這項(xiàng)發(fā)現(xiàn),，將加深人們對(duì)老年黃斑變性的理解,，并有助于開發(fā)有效的治療方法。
    老年黃斑變性這種疾病的一個(gè)早期標(biāo)志是在眼內(nèi)形成一些微小的斑狀物,，被稱作玻璃膜疣（drusen）,。玻璃膜疣被認(rèn)為是該疾病的一種觸發(fā)原因，這種斑狀的玻璃膜疣究竟因何形成,，如何作用,，至今仍然沒有完全了解。
    在此之前人們已經(jīng)知道鋅能促使阿爾茨海默癥患者形成腦斑,，因此,，van Kuijk及其同事根據(jù)邏輯推理，鋅也許也能促使眼中斑狀的玻璃狀疣形成,。隨即他們對(duì)這一設(shè)想進(jìn)行了檢驗(yàn),。Frederickson提出，可把老年黃斑變性當(dāng)作“眼睛的阿爾茨海默癥”,，因?yàn)檫@兩種異常都涉及錯(cuò)誤折疊的淀粉樣蛋白與金屬（象鋅和銅）聚集,，形成被稱作斑的微小的團(tuán)塊。
    研究人員們檢查了從蒙大拿眼睛庫從死去的老年黃斑變性患者處得來的眼睛，這些眼睛在視網(wǎng)膜色素上皮下有一些較大的沉積,。并將它們與類似年齡組的其它死者的眼睛作了比較,，這些眼睛沒有已知眼睛疾病且在黃斑上沒有沉積。實(shí)驗(yàn)中他們使用了由Galveston市Neurobiotex公司的Christopher教授開發(fā)的一種叫ZP-1的試劑,。ZP-1是一種鋅感應(yīng)分子,，在與鋅結(jié)合時(shí)會(huì)發(fā)光，但其只與游離的或結(jié)合松散的鋅結(jié)合,，這種鋅對(duì)造成該疾病特別關(guān)鍵,。
    “van Kuijk博士及其同事的先驅(qū)性工作對(duì)我們理解老年黃斑變性是一項(xiàng)很重要的進(jìn)展。”德州大學(xué)醫(yī)學(xué)分校新設(shè)立的黃斑變性研究中心主任Michael Boulton說道,。 “以鋅為目標(biāo)來使玻璃狀疣逆轉(zhuǎn)或停止生長(zhǎng),，這種可能性很重要。因?yàn)檫@樣做有可能能夠在視網(wǎng)膜細(xì)胞出現(xiàn)不可逆轉(zhuǎn)的損害之前,，及早制止老年黃斑變性,。”

原文出處:

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

背景知識(shí)：

黃斑變性是發(fā)達(dá)國家中老年人失明的主要原因，僅在美國就有成千上萬（在75歲以上的人中有30%的人患?。┑娜耸艿竭@種疾病的折磨,。老年黃斑變性是黃斑疾病，它與視網(wǎng)膜色素上皮細(xì)胞的缺陷有關(guān),，視網(wǎng)膜色素上皮細(xì)胞的淍亡可導(dǎo)致進(jìn)行性失明,。
盡管老年黃斑變性從來不會(huì)導(dǎo)致徹底失明的發(fā)生，但會(huì)使視野的中間部分喪失,。這意味著這種情況會(huì)在閱讀,、辯人、看小物品及駕駛時(shí)導(dǎo)致嚴(yán)重的問題,，這對(duì)患者的生活質(zhì)量是一種沉重的打擊,。這種疾病在女性中比在男性中常見。 通常的危險(xiǎn)因素是家族史和吸煙,。老年黃斑變性有兩種形式,，干性型和濕性型。 干性型的老年黃斑變性意味著視覺細(xì)胞干脆不再起作用,，而濕性型老年黃斑變性則與新血管生長(zhǎng)有關(guān)聯(lián),。 目前對(duì)干性型的老年黃斑變性無法治療，但在治療濕性型的老年黃斑變性方面則取得了相當(dāng)?shù)倪M(jìn)展,，包括使用象阿瓦斯丁和Lucentis等能夠使血管生長(zhǎng)停止的藥物,。 但是，這些治療方法都只適用于患病晚期的患者,，而且它們的效果通常是暫時(shí)的,，并且還有不良反應(yīng)的危險(xiǎn),。