Genetic Profiles of Senescent Corneal and Conjunctival Epithelial Cells in Humans

10-02-2023

“[...] our results from the RNA-Seq experiments show that senescent ocular surface cells, particularly SCj, have abnormal keratin expression patterns [...]”

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BUFFALO, NY- October 2, 2023 – A new priority research paper was published on the cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 18, entitled, “Gene expression signatures of human senescent corneal and conjunctival epithelial cells.”

In this new study, researchers Koji Kitazawa, Akifumi Matsumoto, Kohsaku Numa, Yasufumi Tomioka, Zhixin A. Zhang, Yohei Yamashita, Chie Sotozono, Pierre-Yves Desprez, and Judith Campisi from the Buck Institute for Research on Aging, Kyoto Prefectural University of Medicine and Lawrence Berkeley National Laboratory aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells.

“Here, we induced cellular senescence in human corneal and conjunctival epithelium using X-irradiation, and analyzed gene expression profiles of each cell type to determine the characteristics of senescent ocular surface cells.”

The team 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.

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.

“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.”

Read the full study: DOI: https://doi.org/10.18632/aging.205113 

Corresponding Author: Koji Kitazawa & Judith Campisi - kkitazaw@koto.kpu-m.ac.jp & jcampisi@buckinstitute.org 

Keywords: cellular senescence, cornea, conjunctiva, Stevens-Johnson syndrome, limbal stem cell deficiency

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About Aging-US:

Cancer and aging are two sides of age-related tumorigenesis.

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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