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Study examines human senescent corneal and conjunctival epithelial cells

RNA sequencing analysis has shown that senescent ocular surface cells, particularly conjunctival epithelial cells, show abnormal keratin expression signatures, thus highlighting their potential role in various severe diseases and pathologies of the ocular surface

Ageing is a natural process and, what with the world population growing older, the scientific community has paid increasing attention to common health conditions associated with old age.

A better understanding of the biological changes associated with ageing is crucial for developing new successful treatments.

In this regard, a team of researchers from the Buck Institute for Research on Aging, the Lawrence Berkeley National Laboratory (United States), and the Kyoto Prefectural University of Medicine (Japan) have published a study on the gene expression signatures of human senescent corneal and conjunctival epithelial cells in Aging, a peer-reviewed ageing research journal.

The team, which is composed of 9 researchers, chose to focus on senescent cells, even though many explanations have been proposed throughout the years for biological age-related changes, including genomic instability, mitochondrial dysfunction and altered intercellular communication.

Senescent cells not only accumulate during ageing, contributing to pathological conditions, but, according to recent research, they also acquire a proinflammatory phenotype, also known as SASP (senescent-associated secretory phenotype), which, over time, can alter the surrounding microenvironment. For these reasons, researchers focused on understanding the phenotype of senescent cells through the generation of several cellular culture models.

Among the many available methods, the team chose to induce cellular senescence in corneal epithelium and conjunctival cells using X-irradiation and studied gene expression profiles of each cell to determine the characteristics of senescent ocular surface cells.

Determining the role of such cells can help us better understand age-related ocular surface diseases, such as dry eye disease (DED) and limbal stem cell deficiency (LSCD).

First, researchers focused on the morphology of the analysed cells, which looked rather elongated, flattened, and bigger than non-irradiated cells.

Secondly, they studied the activity of β-Galactosidase (SA-β-gal) associated with senescence, which showed significantly higher levels in irradiated cells.

Then, an analysis of cellular proliferation and homeostasis was conducted, with cells displaying decreased proliferation levels.

Afterwards, p16 and p21 senescence markers were examined, both of which were significantly higher in irradiated cells.

Finally, RNA sequencing analysis (RNA-Seq) was carried out in order to compare gene expression profiles between senescent and non-senescent cells.

This last analysis not only confirmed high expressions of typical markers of cellular senescence, but also the presence of the aforementioned SASP.

Additionally, alteration in keratin expression patterns was observed, suggesting the involvement of senescent cells in the differentiation abnormalities of pathological tissues. This finding indicates that ocular surface cells in patients with LSCD, if exposed to acute destructive inflammation, are subject to high levels of stress, which accelerate the ageing process.

Another important finding is that senescent cells can exhibit different profiles of SASP depending on the specific factor that induced cellular senescence. Therefore, further investigation is required to study the impact of other factors, such as UVA and UVB rays.

Overall, the RNA-sequencing analysis shows that senescent cells of the ocular surface, especially conjunctival cells, have abnormal keratin expression patterns, highlighting their involvement in many serious pathologies of the ocular surface.


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