Gene expression signatures of human senescent corneal and conjunctival epithelial cells

人类衰老角膜和结膜上皮细胞的基因表达特征

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作者:Koji Kitazawa, Akifumi Matsumoto, Kohsaku Numa, Yasufumi Tomioka, Zhixin A Zhang, Yohei Yamashita, Chie Sotozono, Pierre-Yves Desprez, Judith Campisi

Conclusion

This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.

Methods

We examined cell morphology, senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated.

Purpose

This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells.

Results

X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-β-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation.

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