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Priority Research Paper|Volume 15, Issue 18|pp 9238—9249

Gene expression signatures of human senescent corneal and conjunctival epithelial cells

Koji Kitazawa1,2, Akifumi Matsumoto2, Kohsaku Numa1,2, Yasufumi Tomioka2, Zhixin A. Zhang1, Yohei Yamashita2, Chie Sotozono2, Pierre-Yves Desprez1, Judith Campisi1,3
  • 1Buck Institute for Research on Aging, Novato, CA 94945, USA
  • 2Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 6020841, Japan
  • 3Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
Received: July 18, 2023Accepted: September 17, 2023Published: September 28, 2023
https://doi.org/10.18632/aging.205113

Copyright: © 2023 Kitazawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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

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.

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.

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.