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渗出性年龄相关性黄斑变性是否涉及低炎症反应?与基底沉积物相关的年龄相关性黄斑变性的形态学和免疫组织化学分析。

Are low inflammatory reactions involved in exudative age-related macular degeneration? Morphological and immunhistochemical analysis of AMD associated with basal deposits.

作者信息

Lommatzsch A, Hermans P, Müller K D, Bornfeld N, Bird A C, Pauleikhoff D

机构信息

Department of Ophthalmology and Ophtha-Lab, St. Franziskus Hospital Münster, Münster, Germany.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2008 Jun;246(6):803-10. doi: 10.1007/s00417-007-0749-4. Epub 2008 Apr 15.

Abstract

PURPOSE

Basal laminar and linear deposits (BLD) are associated with the development of choroidal neovascularization (CNV). Therefore, analysis of BLD composition may provide further information concerning the pathogenesis of BLD and CNV in age-related macular degeneration (AMD).

METHODS

BLD in 25 specimens of surgically removed CNV were examined, using histochemical and immunohistochemical methods, for extracellular matrix proteins and their modulating enzymes, and for cell markers and proteins involved in inflammatory processes. In addition, ultrastructural electron microscopic analysis (EM) was performed.

RESULTS

The chemical and structural composition of all the BLD was similar. Only the inner aspect of the BLD contained laminin and collagen IV, which corresponded to a new RPE basal lamina upon EM analysis. The extracellular matrix protein predominantly found in all layers of BLD was vitronectin, which was seen as a homogeneous material within the BLD upon EM analysis. The metalloproteinases MMP-2 and MMP-9 could only be detected in the inner aspect, while MMP-7 and TIMP-3 were observed predominantly in the outer aspect of BLD. In this area, staining for phospholipids and less intensely for neutral lipids was also visible. The labelling of complement complexes C3 and C5b-9 was intensely positive, and vascular endothelial growth factor (VEGF) was detected in all BLDs.

CONCLUSIONS

Diffuse deposits such as BLD appear consistently with the development of CNV in AMD. They consist of extracellular matrix components and predominantly vitronectin. However, activated complement and VEGF could also be detected. The results of the current study may support the hypothesis that inflammatory processes are involved in the pathogenesis of BLD and CNV in AMD.

摘要

目的

基底膜样和线性沉积物(BLD)与脉络膜新生血管(CNV)的发生相关。因此,分析BLD的组成可能为年龄相关性黄斑变性(AMD)中BLD和CNV的发病机制提供更多信息。

方法

使用组织化学和免疫组织化学方法,对25个手术切除的CNV标本中的BLD进行检查,以检测细胞外基质蛋白及其调节酶,以及参与炎症过程的细胞标志物和蛋白质。此外,还进行了超微结构电子显微镜分析(EM)。

结果

所有BLD的化学和结构组成相似。仅BLD的内侧含有层粘连蛋白和IV型胶原,在EM分析中这对应于一层新的视网膜色素上皮(RPE)基底膜。在BLD的所有层中主要发现的细胞外基质蛋白是玻连蛋白,在EM分析中其在BLD内表现为均匀物质。金属蛋白酶MMP-2和MMP-9仅在内侧被检测到,而MMP-7和TIMP-3主要在BLD的外侧被观察到。在该区域,磷脂染色可见,中性脂质染色较弱。补体复合物C3和C5b-9的标记呈强阳性,并且在所有BLD中均检测到血管内皮生长因子(VEGF)。

结论

诸如BLD之类的弥漫性沉积物与AMD中CNV的发生一致。它们由细胞外基质成分组成,主要是玻连蛋白。然而,也可检测到活化的补体和VEGF。本研究结果可能支持炎症过程参与AMD中BLD和CNV发病机制的假说。

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