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翼状胬肉发病机制:表达基质金属蛋白酶的异常角膜缘上皮基底细胞侵袭角膜

Pterygia pathogenesis: corneal invasion by matrix metalloproteinase expressing altered limbal epithelial basal cells.

作者信息

Dushku N, John M K, Schultz G S, Reid T W

机构信息

Department of Ophthalmology, Kaiser Permanente Medical Center, Sacramento, CA 95815, USA.

出版信息

Arch Ophthalmol. 2001 May;119(5):695-706. doi: 10.1001/archopht.119.5.695.

DOI:10.1001/archopht.119.5.695
PMID:11346397
Abstract

OBJECTIVE

To assess the potential role of matrix metalloproteinases (MMPs) in the pathogenesis of pterygia by comparing the immunolocalization patterns of MMPs in altered limbal basal stem cells, activated fibroblasts, and areas of elastotic degeneration adjacent to the pterygia.

METHODS

Nine primary and 1 recurrent pterygia along with normal superior limbal-conjunctival tissue and cornea were immunostained with mouse monoclonal antibodies specific for MMP-1, MMP-2, MMP-3, MMP-9, membrane type 1 (MT1)-MMP (MMP-14), and membrane type 2-MMP (MMP-15).

RESULTS

Normal conjunctival, limbal, and corneal cells lacked significant immunostaining except for cell surface MT1-MMP. In contrast, altered limbal basal epithelial cells of the 9 primary and 1 recurrent pterygia immunostained for all 6 MMPs. Activated and altered fibroblasts associated with the pterygia immunostained primarily for MMP-1. In contrast, stromal areas of elastotic degeneration (pingueculae) showed variable immunostaining of MMPs.

CONCLUSIONS

Altered limbal basal epithelial cells (pterygium cells) immunostained for multiple types of MMPs in contrast to normal conjunctival, limbal, and corneal cells. The pterygium cells invading over Bowman's layer produce elevated MMP-1, MMP-2, and MMP-9 expression, which probably are the main MMPs responsible for the dissolution of Bowman's layer. Pterygium cells may also cause activation of fibroblasts at the head of the pterygium, leading to the initial cleavage of fibrillar collagen in Bowman's layer by the production of MMP-1. Altered fibroblasts in areas of elastotic degeneration (pingueculae) trailing behind the pterygium constitute a second type of tumor, which is noninvasive.

CLINICAL RELEVANCE

These data of altered MMP expression support the concept that altered basal limbal epithelial cells play a key role in the formation and migration of a pterygium.

摘要

目的

通过比较基质金属蛋白酶(MMPs)在翼状胬肉中改变的角膜缘基底干细胞、活化的成纤维细胞以及翼状胬肉相邻的弹性组织变性区域中的免疫定位模式,评估MMPs在翼状胬肉发病机制中的潜在作用。

方法

采用针对MMP-1、MMP-2、MMP-3、MMP-9、膜型1(MT1)-MMP(MMP-14)和膜型2-MMP(MMP-15)的小鼠单克隆抗体,对9例原发性和1例复发性翼状胬肉以及正常的上方角膜缘结膜组织和角膜进行免疫染色。

结果

除细胞表面的MT1-MMP外,正常结膜、角膜缘和角膜细胞缺乏明显的免疫染色。相比之下,9例原发性和1例复发性翼状胬肉中改变的角膜缘基底上皮细胞对所有6种MMPs均呈免疫染色阳性。与翼状胬肉相关的活化和改变的成纤维细胞主要对MMP-1呈免疫染色阳性。相比之下,弹性组织变性(睑裂斑)的基质区域对MMPs的免疫染色呈多样化。

结论

与正常结膜、角膜缘和角膜细胞相比,改变的角膜缘基底上皮细胞(翼状胬肉细胞)对多种类型的MMPs呈免疫染色阳性。侵入Bowman层上方的翼状胬肉细胞MMP-1、MMP-2和MMP-9表达升高,这可能是导致Bowman层溶解的主要MMPs。翼状胬肉细胞还可能导致翼状胬肉头部的成纤维细胞活化,通过产生MMP-1导致Bowman层中的纤维状胶原初步裂解。在翼状胬肉后方的弹性组织变性(睑裂斑)区域中改变的成纤维细胞构成了第二种肿瘤类型,其为非侵袭性。

临床意义

这些MMP表达改变的数据支持了角膜缘基底上皮细胞改变在翼状胬肉形成和迁移中起关键作用的概念。

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