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与衰老及年龄相关性黄斑变性相关的玻璃膜疣含有一些蛋白质,这些蛋白质与动脉粥样硬化、弹性组织变性、淀粉样变性及致密物沉积病相关的细胞外沉积物中的蛋白质相同。

Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease.

作者信息

Mullins R F, Russell S R, Anderson D H, Hageman G S

机构信息

The University of Iowa Center for Macular Degeneration, Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa 52242, USA.

出版信息

FASEB J. 2000 May;14(7):835-46.

PMID:10783137
Abstract

Age-related macular degeneration (AMD), a blinding disorder that compromises central vision, is characterized by the accumulation of extracellular deposits, termed drusen, between the retinal pigmented epithelium and the choroid. Recent studies in this laboratory revealed that vitronectin is a major component of drusen. Because vitronectin is also a constituent of abnormal deposits associated with a variety of diseases, drusen from human donor eyes were examined for compositional similarities with other extracellular disease deposits. Thirty-four antibodies to 29 different proteins or protein complexes were tested for immunoreactivity with hard and soft drusen phenotypes. These analyses provide a partial profile of the molecular composition of drusen. Serum amyloid P component, apolipoprotein E, immunoglobulin light chains, Factor X, and complement proteins (C5 and C5b-9 complex) were identified in all drusen phenotypes. Transcripts encoding some of these molecules were also found to be synthesized by the retina, retinal pigmented epithelium, and/or choroid. The compositional similarity between drusen and other disease deposits may be significant in view of the recently established correlation between AMD and atherosclerosis. This study suggests that similar pathways may be involved in the etiologies of AMD and other age-related diseases.

摘要

年龄相关性黄斑变性(AMD)是一种导致失明的疾病,会损害中心视力,其特征是在视网膜色素上皮和脉络膜之间积累称为玻璃膜疣的细胞外沉积物。本实验室最近的研究表明,玻连蛋白是玻璃膜疣的主要成分。由于玻连蛋白也是与多种疾病相关的异常沉积物的组成成分,因此对来自人类供体眼睛的玻璃膜疣进行了检查,以确定其与其他细胞外疾病沉积物在成分上的相似性。针对29种不同蛋白质或蛋白质复合物的34种抗体被检测与硬性和软性玻璃膜疣表型的免疫反应性。这些分析提供了玻璃膜疣分子组成的部分概况。在所有玻璃膜疣表型中均鉴定出血清淀粉样蛋白P成分、载脂蛋白E、免疫球蛋白轻链、凝血因子X和补体蛋白(C5和C5b-9复合物)。还发现视网膜、视网膜色素上皮和/或脉络膜会合成编码其中一些分子的转录本。鉴于最近确立的AMD与动脉粥样硬化之间的相关性,玻璃膜疣与其他疾病沉积物在成分上的相似性可能具有重要意义。这项研究表明,AMD和其他年龄相关性疾病的病因可能涉及相似的途径。

相似文献

1
Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease.与衰老及年龄相关性黄斑变性相关的玻璃膜疣含有一些蛋白质,这些蛋白质与动脉粥样硬化、弹性组织变性、淀粉样变性及致密物沉积病相关的细胞外沉积物中的蛋白质相同。
FASEB J. 2000 May;14(7):835-46.
2
Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis).食蟹猴(猕猴属)两种不同形式黄斑变性中玻璃膜疣的分子组成及抗视网膜自身免疫的可能作用。
FASEB J. 2005 Oct;19(12):1683-5. doi: 10.1096/fj.04-3525fje. Epub 2005 Aug 12.
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Molecular composition of drusen as related to substructural phenotype.与亚结构表型相关的玻璃膜疣的分子组成
Mol Vis. 1999 Nov 3;5:28.
4
Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas.β-淀粉样蛋白在一些年龄相关性黄斑变性视网膜的玻璃膜疣中被发现,但在正常视网膜的玻璃膜疣中未被发现。
Mol Vis. 2003 May 14;9:184-90.
5
Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis.与肾小球肾炎相关的玻璃膜疣的结构与组成:补体激活在玻璃膜疣生物发生中的作用启示
Eye (Lond). 2001 Jun;15(Pt 3):390-5. doi: 10.1038/eye.2001.142.
6
Characterization of beta amyloid assemblies in drusen: the deposits associated with aging and age-related macular degeneration.玻璃膜疣中β淀粉样蛋白聚集体的特征:与衰老及年龄相关性黄斑变性相关的沉积物
Exp Eye Res. 2004 Feb;78(2):243-56. doi: 10.1016/j.exer.2003.10.011.
7
Drusen are Cold Spots for Proteolysis: Expression of Matrix Metalloproteinases and Their Tissue Inhibitor Proteins in Age-related Macular Degeneration.玻璃膜疣是蛋白水解的冷区:基质金属蛋白酶及其组织抑制蛋白在年龄相关性黄斑变性中的表达
Exp Eye Res. 2002 Jan;74(1):141-54. doi: 10.1006/exer.2001.1112.
8
Synaptic pathology, altered gene expression, and degeneration in photoreceptors impacted by drusen.受玻璃膜疣影响的光感受器中的突触病理学、基因表达改变和变性。
Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4788-95. doi: 10.1167/iovs.05-0767.
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Vitronectin is a constituent of ocular drusen and the vitronectin gene is expressed in human retinal pigmented epithelial cells.玻连蛋白是眼玻璃膜疣的一种成分,且玻连蛋白基因在人视网膜色素上皮细胞中表达。
FASEB J. 1999 Mar;13(3):477-84. doi: 10.1096/fasebj.13.3.477.
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A potential role for immune complex pathogenesis in drusen formation.免疫复合物发病机制在玻璃膜疣形成中的潜在作用。
Exp Eye Res. 2000 Apr;70(4):441-9. doi: 10.1006/exer.1999.0798.

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