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人角膜基底膜的异质性:IV型胶原蛋白和层粘连蛋白亚型表达的地形差异

Human corneal basement membrane heterogeneity: topographical differences in the expression of type IV collagen and laminin isoforms.

作者信息

Ljubimov A V, Burgeson R E, Butkowski R J, Michael A F, Sun T T, Kenney M C

机构信息

Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, UCLA Medical School, USA.

出版信息

Lab Invest. 1995 Apr;72(4):461-73.

PMID:7723285
Abstract

BACKGROUND

The corneal epithelium converges at the peripheral zone (limbus) with the conjunctival epithelium, forming a continuous sheet with phenotypically distinct regions--central, limbal, and conjunctival. The epithelial basement membrane (EBM) is important for corneal functions and cell adhesion, but its regional composition is poorly understood. Current literature is controversial as to the occurrence of type IV collagen in the cornea. The aim of this study was to investigate in detail corneal basement membrane (BM) composition and correlate it with the differentiation state of contributing cells.

EXPERIMENTAL DESIGN

Adult human corneas (N = 8) were cryosectioned and analyzed by immunofluorescence with antibodies to 15 BM components and to keratin 3, a marker of corneal epithelial differentiation.

RESULTS

A novel type of spatial heterogeneity ("horizontal") in the EBM composition was found between the central cornea, limbus, and conjunctiva. Central EBM had type IV collagen alpha 3-alpha 5 chains, whereas limbal and conjunctival EBM contained alpha 1-alpha 2 chains and also laminin alpha 2 and beta 2 chains. Limbal EBM in addition had alpha 5(IV) chain. Laminin-1 (alpha 1 beta 1 gamma 1), laminin-5 (alpha 3 beta 3 gamma 2), perlecan, fibronectin, entactin/nidogen, and type VII collagen were seen in the entire EBM. Another novel type of BM heterogeneity ("vertical") was typical for the corneal Descemet's membrane: its stromal face had alpha 1(IV) and alpha 2(IV) chains and fibronectin, whereas alpha 3(IV)-alpha 5(IV) chains, entactin/nidogen, laminin-1, and perlecan were present on the endothelial face.

CONCLUSIONS

Type IV collagen controversy is the result of the shifts of isoforms in the limbus and conjunctiva. These shifts and the appearance of additional laminins in the limbus may be related to the differentiation state of corneal cells contributing to the EBM formation. Novel types of BM heterogeneity in the human cornea are described: regional (horizontal) in the EBM and vertical in the Descemet's membrane. The first one may be a common feature of converging complex epithelia, whereas the second one may be another unique property of the Descemet's membrane.

摘要

背景

角膜上皮在周边区域(角膜缘)与结膜上皮相汇合,形成一个具有表型不同区域(中央、角膜缘和结膜)的连续薄片。上皮基底膜(EBM)对角膜功能和细胞黏附很重要,但其区域组成了解甚少。目前关于角膜中IV型胶原的存在情况,文献存在争议。本研究的目的是详细研究角膜基底膜(BM)的组成,并将其与相关细胞的分化状态联系起来。

实验设计

对8例成人人类角膜进行冷冻切片,并用针对15种BM成分和角蛋白3(角膜上皮分化标志物)的抗体进行免疫荧光分析。

结果

在中央角膜、角膜缘和结膜之间的EBM组成中发现了一种新型的空间异质性(“水平”)。中央EBM含有IV型胶原α3 - α5链,而角膜缘和结膜EBM含有α1 - α2链以及层粘连蛋白α2和β2链。角膜缘EBM还含有α5(IV)链。在整个EBM中可见层粘连蛋白-1(α1β1γ1)、层粘连蛋白-5(α3β3γ2)、基底膜聚糖、纤连蛋白、巢蛋白/巢素和VII型胶原。另一种新型的BM异质性(“垂直”)是角膜后弹力层的典型特征:其基质面含有α1(IV)和α2(IV)链以及纤连蛋白,而在内皮面存在α3(IV) - α5(IV)链、巢蛋白/巢素、层粘连蛋白-1和基底膜聚糖。

结论

IV型胶原的争议是角膜缘和结膜中异构体变化的结果。这些变化以及角膜缘中额外层粘连蛋白的出现可能与参与EBM形成的角膜细胞的分化状态有关。描述了人类角膜中新型的BM异质性:EBM中的区域(水平)异质性和后弹力层中的垂直异质性。第一种可能是汇聚的复层上皮的共同特征,而第二种可能是后弹力层的另一个独特特性。

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