Soluble and mature amyloid fibrils in drusen deposits.
Soluble and mature amyloid fibrils in drusen deposits.
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DOI：
10.1167/iovs.09-4207
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发表时间：
2010-03
影响因子：
4.4
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Isas JM;Luibl V;Johnson LV;Kayed R;Wetzel R;Glabe CG;Langen R;Chen J
玻璃疣是受年龄相关性黄斑变性影响的眼睛的标志。先前的研究表明玻璃疣含有非纤维状淀粉样结构，使用构象特异性抗体。本研究旨在评估玻璃疣中是否存在其他淀粉样结构。将来自人供体眼睛的切片与M204（一种识别非纤维状寡聚体的单克隆抗体）、OC（一种识别不同分子量的淀粉样蛋白纤维的多克隆抗体）以及WO 1和WO 2（一种对成熟淀粉样蛋白纤维具有特异性反应性的单克隆抗体）反应。电子显微镜作为一种独立的手段来调查玻璃疣中淀粉样纤维的存在。使用M204抗体验证非纤维状寡聚体的存在。OC和WO抗体染色范围广泛的囊泡结构。OC反应性与Aβ免疫反应性广泛重叠，而Aβ反应性与WO抗体反应性之间存在部分重叠。淀粉样纤维的存在也进行了研究，通过电子显微镜。这些数据揭示了玻璃疣中广泛的淀粉样结构的存在。这些结果是有意义的，因为已知淀粉样蛋白的特定构象形式在多种神经退行性疾病中是致病的。这些结构的沉积可能导致视网膜色素上皮的局部毒性或诱导局部炎症事件，其有助于玻璃疣生物发生和AMD的发病机制。
Drusen are a hallmark of eyes affected with age-related macular degeneration. A previous study showed drusen to contain non-fibrillar amyloid structures using a conformational specific antibody. This study was undertaken to assess the presence of additional amyloid structures in drusen. Sections from human donor eyes were reacted with M204, a monoclonal antibody that recognizes nonfibrillar oligomers; OC, a polyclonal antibody that recognizes amyloid fibrils of varying molecular weight, and WO1 and WO2, which are monoclonal antibodies that are specifically reactive to mature amyloid fibrils. Electron microscopy was used as an independent means to investigate the presence of amyloid fibrils in drusen. The presence of nonfibrillar oligomers was verified using the M204 antibody. OC and WO antibodies stained a wide spectrum of vesicular structures. OC reactivity showed extensive overlap with Aβ immunoreactivity, while partial overlap was seen between Aβ reactivity and that of the WO antibodies. The presence of amyloid fibrils was also investigated by electron microscopy. These data reveal the presence of a wide spectrum of amyloid structures in drusen. These results are significant given that specific conformational forms of amyloid are known to be pathogenic in a variety of neurodegenerative diseases. Deposition of these structures may lead to local toxicity of the retinal pigmented epithelium or induction of local inflammatory events that contribute to drusen biogenesis and the pathogenesis of AMD.
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影响因子：
15.1
作者：
Kayed R;Head E;Sarsoza F;Saing T;Cotman CW;Necula M;Margol L;Wu J;Breydo L;Thompson JL;Rasool S;Gurlo T;Butler P;Glabe CG
通讯作者：
Glabe CG
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
1.8
作者：
Ding, Jin-Dong;Lin, John;Rickman, Catherine Bowes
通讯作者：
Rickman, Catherine Bowes
DOI：
10.1073/pnas.022662599
发表时间：
2002-02-05
影响因子：
11.1
作者：
O'Nuallain, B;Wetzel, R
通讯作者：
Wetzel, R
影响因子：
13.8
作者：
Dobson, CM
通讯作者：
Dobson, CM