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原发性开角型青光眼患者视神经头中弹性蛋白 mRNA 表达的激活。

Activation of elastin mRNA expression in human optic nerve heads with primary open-angle glaucoma.

机构信息

Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, U.S.A.

出版信息

J Glaucoma. 1994 Fall;3(3):214-25.

Abstract

Elastin is the major protein of elastic fibers and is responsible for the elastic recoil. Elastic fibers are a major component of the extracellular matrix in the human lamina cribrosa and undergo marked changes in primary open-angle glaucoma. Ultrastructural and immunocytochemical analysis demonstrated fragmentation of elastic fibers, accumulation of nonfibrillar elastic material, and bundles of microfibrils in the core of the cribriform plates in primary open-angle glaucoma. The changes in elastic fibers increased with the progression of the disease and strongly suggested abnormal biosynthesis, degradation of elastic fibers, or both. In this study, we used in situ hybridization and reverse transcriptase-polymerase chain reaction to localize and detect expression of elastin messenger RNA (mRNA) in human optic nerve heads with primary open-angle glaucoma and age-matched normal controls. The major finding of this study is the demonstration of elastin mRNA in the lamina cribrosa cells of optic nerve heads with primary open-angle glaucoma and the absence of this message in normal donors. Several studies have demonstrated a concordance between levels of elastin and relative levels of elastin mRNA. Our findings indicate de novo synthesis of elastin in the compressed lamina cribrosa in primary open-angle glaucoma. Synthesis of abnormal elastic fibers must alter the mechanical properties of the lamina cribrosa and may lead to compression, remodeling, and rearrangement of the cribriform plates characteristic of glaucomatous cupping.

摘要

弹性蛋白是弹性纤维的主要蛋白,负责弹性回弹。弹性纤维是人类筛板细胞外基质的主要成分,在原发性开角型青光眼中有明显的变化。超微结构和免疫细胞化学分析显示,在原发性开角型青光眼的筛板核心处,弹性纤维断裂,无纤维弹性物质堆积,微纤维束形成。弹性纤维的变化随着疾病的进展而增加,强烈提示异常的生物合成、弹性纤维降解或两者兼有。在这项研究中,我们使用原位杂交和逆转录聚合酶链反应,在原发性开角型青光眼和年龄匹配的正常对照组的人视神经头部定位和检测弹性蛋白信使 RNA(mRNA)的表达。这项研究的主要发现是证明了原发性开角型青光眼视神经头部筛板细胞中的弹性蛋白 mRNA,而在正常供体中则没有这种信息。有几项研究表明,弹性蛋白的水平与弹性蛋白 mRNA 的相对水平之间存在一致性。我们的研究结果表明,在原发性开角型青光眼的受压筛板中,弹性蛋白的从头合成。异常弹性纤维的合成必然改变筛板的力学性能,并可能导致青光眼杯状凹陷的特征性筛板压缩、重塑和重排。

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