Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up

Sumako Kameishi, Hiroaki Sugiyama, Masayuki Yamato, Yoshikazu Sado, Hideo Namiki, Takashi Kato, Teruo Okano

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    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 opacification. 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, α1(IV) and α2(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, α1(IV) and α2(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 α1(IV) and α2(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.

    Original languageEnglish
    Pages (from-to)168-179
    Number of pages12
    JournalLaboratory Investigation
    Volume95
    Issue number2
    DOIs
    Publication statusPublished - 2015 Mar 3

    Fingerprint

    Conjunctiva
    Basement Membrane
    Cornea
    Epithelial Cells
    Cell Membrane
    Stem Cell Niche
    Collagen
    Keratin-12
    Limbus Corneae
    Corneal Neovascularization
    Anatomic Models
    Corneal Epithelium
    Vimentin
    Mitosis
    Islands
    Stem Cells
    Epithelium
    Rabbits
    Phenotype

    ASJC Scopus subject areas

    • Pathology and Forensic Medicine
    • Cell Biology
    • Molecular Biology

    Cite this

    Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up. / Kameishi, Sumako; Sugiyama, Hiroaki; Yamato, Masayuki; Sado, Yoshikazu; Namiki, Hideo; Kato, Takashi; Okano, Teruo.

    In: Laboratory Investigation, Vol. 95, No. 2, 03.03.2015, p. 168-179.

    Research output: Contribution to journalArticle

    Kameishi, Sumako ; Sugiyama, Hiroaki ; Yamato, Masayuki ; Sado, Yoshikazu ; Namiki, Hideo ; Kato, Takashi ; Okano, Teruo. / Remodeling of epithelial cells and basement membranes in a corneal deficiency model with long-term follow-up. In: Laboratory Investigation. 2015 ; Vol. 95, No. 2. pp. 168-179.
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