June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
The senescent characteristics of UV-A exposed human corneal endothelial cells.
Author Affiliations & Notes
  • Kohsaku Numa
    Buck Institute for Research on Aging, Novato, California, United States
    Kyoto Furitsu Ika Daigaku, Kyoto, Kyoto, Japan
  • Koji Kitazawa
    Buck Institute for Research on Aging, Novato, California, United States
    Kyoto Furitsu Ika Daigaku, Kyoto, Kyoto, Japan
  • Pierre-Yves Desprez
    Buck Institute for Research on Aging, Novato, California, United States
  • Judith Campisi
    Buck Institute for Research on Aging, Novato, California, United States
    E O Lawrence Berkeley National Laboratory, Berkeley, California, United States
  • Footnotes
    Commercial Relationships   Kohsaku Numa None; Koji Kitazawa None; Pierre-Yves Desprez None; Judith Campisi Unity Biotechnology, Code O (Owner)
  • Footnotes
    Support  NIH AG009909, NIH AG017242
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 644. doi:
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      Kohsaku Numa, Koji Kitazawa, Pierre-Yves Desprez, Judith Campisi; The senescent characteristics of UV-A exposed human corneal endothelial cells.. Invest. Ophthalmol. Vis. Sci. 2023;64(8):644.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Oxidative stress due to ultraviolet-A light (UV-A) is known to be one of causes to develop Fuchs endothelial corneal dystrophy (FECD). It is widely recognized that premature senescence is part of the cellular response in FECD pathogenesis. This study is aimed to investigate the senescent characteristics of corneal endothelial cells (CEnCs) which were exposed to UV-A, compared to senescent CEnCs which were exposed to X-rays.

Methods : Human primary CEnCs were obtained from donor corneas. Human CEnCs were irradiated with 2.5 or 5.0 J/cm2 UV-A or 10Gy X-rays to induce cell senescence and then cultured for 10 days. The senescent characteristics were analyzed by senescence-associated ß-galactosidase (SA ß-gal) staining, Ed-U labeling, and senescent-associated gene expression.

Results : CEnCs exposed to 2.5 J/cm2 UV-A did not stop proliferating. CEnCs which were exposed to 5.0 J/cm2 UV-A and 10Gy X-ray displayed bigger size as the culture period goes on, and cells stopped proliferating. CEnCs exposed to 5.0 J/cm2 UV-A and 10Gy X-ray showed significantly high SA ß-gal activity, low Ed-U labelling, and elevated gene expression levels of p16 and p21, suggesting that these CEnCs became senescent. Inflammatory cytokines and chemokines, such as IL-6, IL-1 ß, GDF15, CCL5, CXCL9 were significantly elevated in these senescent CEnCs.

Conclusions : UV-A induced cellular senescence is dose-dependent in CEnCs. We conclude that 5.0 J/cm2 UV-A exposed CEnCs became senescent cells, that could contribute the pathophysiology of FECD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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