Mullins R F, Russell S R, Anderson D H, Hageman G S
The University of Iowa Center for Macular Degeneration, Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa 52242, USA.
FASEB J. 2000 May;14(7):835-46.
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.
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。