4.6 Article

Gene expression signatures of human senescent corneal and conjunctival epithelial cells

Journal

AGING-US
Volume 15, Issue 18, Pages 9238-9249

Publisher

IMPACT JOURNALS LLC

Keywords

cellular senescence; cornea; conjunctiva; Stevens-Johnson syndrome; limbal stem cell deficiency

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This study investigated the senescent phenotypes of human corneal and conjunctival epithelial cells and found the characteristics of senescence in these cells. The study also revealed the potential involvement of senescent cells in the pathogenesis of ocular surface diseases.
Purpose: This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells. Methods: We examined cell morphology, senescence-associated 13-galactosidase (SA -13-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. Results: X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA -13-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. 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.

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