Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up
Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up
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DOI：
10.1038/labinvest.2014.146
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发表时间：
2015-02-01
影响因子：
5
通讯作者：
Okano, Teruo
中科院分区：
文献类型：
--
作者：
Kameishi, Sumako;Sugiyama, Hiroaki;Okano, Teruo
眼表由角膜、结膜和位于角膜和结膜之间过渡区的角膜缘组成。角膜上皮细胞是由角膜缘的角膜上皮干细胞有丝分裂产生的。本研究通过手术切除表达细胞角蛋白12 （K12）的角膜上皮和角膜缘上皮制备兔角膜缺损模型。手术后，表达k13的结膜上皮迁移到角膜表面并完全覆盖角膜表面，导致新生血管形成和角膜安抚。然而，在手术后24周和48周，表达k12的角膜样细胞在模型眼表面重新出现。这些细胞形成一个岛，被侵入的结膜包围，并从角膜缘分离出来。有趣的是，在24周的模型表面，α 1 （IV）和α 2（IV）胶原链连续沉积在整个基底膜上，包括角膜样细胞下的基底膜，而α 1 （IV）和α 2（IV）胶原链通常存在于天然角膜缘和结膜的基底膜上，而不是角膜中。相比之下，在48周的模型表面，角膜样细胞中央下方的基底膜上没有α 1 （IV）和α 2（IV）胶原链，它们位于侵入性结膜下方以及角膜样细胞与侵入性结膜之间的过渡区，其分布与天然眼基底膜相似。此外，K12、K14、p63、vimentin、α 1 （IV）和α 2（IV）胶原链都存在于48周模型表面的过渡区，这些胶原链都位于天然边缘。因此，在48周的模型表面似乎重建了一个边缘样结构作为干细胞生态位。本研究将有助于了解人类角膜缺陷、上皮细胞表型与基底膜组成的关系以及上皮干细胞生态位。
The ocular surface consists of the cornea, conjunctiva, and the limbus that is located in the transitional zone between the cornea and conjunctiva. The corneal epithelial cells are generated through the mitosis of corneal epithelial stem cells in the limbus. This study investigated a rabbit corneal deficiency model prepared by the surgical removal of the corneal and limbal epithelia, which express cytokeratin 12 (K12). After the surgery, K13-expressing conjunctival epithelium migrated onto the corneal surface and completely covered the surface, leading to neovascularization and corneal pacification. However, at 24 and 48 weeks after the surgery, K12-expressing cornea-like cells reappeared on the model ocular surface. These cells formed an island surrounded by invaded conjunctiva and were isolated from the limbus. Interestingly, in the 24-week model surface, alpha 1 (IV) and alpha 2(IV) collagen chains, which are normally found in the basement membrane of the native limbus and conjunctiva, and not in the cornea, were continuously deposited throughout the entire basement membrane, including the basement membrane under cornea-like cells. By contrast, in the 48-week model surface, alpha 1 (IV) and alpha 2(IV) collagen chains were absent from the basement membrane beneath the central part of cornea-like cells and were localized below the invaded conjunctiva and the transitional zone between cornea-like cells and the invaded conjunctiva, which had similar distribution to the native ocular basement membrane. Moreover, K12, K14, p63, vimentin, and alpha 1 (IV) and alpha 2(IV) collagen chains, which are colocalized in the native limbus, were all present at the transitional zone of the 48-week model surface. Therefore, a limbus-like structure appeared to be reconstructed on the surface of the 48-week model as a stem cell niche. This study should aid in the understanding of human corneal deficiency, the correlation between the epithelial cell phenotype and the composition of the basement membrane, and the epithelial stem cell niche.