Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury

Area of Science:

• Ocular toxicology
• Cellular senescence
• Molecular biology

Background:

• Mustard gas keratopathy (MGK) is a severe ocular complication of sulfur mustard exposure.
• Cellular senescence is increasingly recognized as a contributor to mustard gas toxicity.
• Mitogen-activated protein kinase (MAPK) signaling is implicated in stress responses.

Purpose of the Study:

• To investigate cellular senescence and MAPK signaling in nitrogen mustard (NM)-induced corneal injury.
• To evaluate the therapeutic potential of p38-MAPK inhibition in NM-induced corneal damage.

Main Methods:

• In vitro exposure of human corneal cells (P-HCECs, hcMSCs, HCLE) to varying NM concentrations.
• Assessment of senescence markers (Ki67, p16, p21) and MAPK pathway activation.
• Treatment with a selective p38-MAPK inhibitor post-NM exposure.

Main Results:

• NM exposure induced a dose-dependent increase in cellular senescence.
• Elevated p16 and p21 mRNA levels and reduced Ki67 expression were observed.
• MAPK pathway, specifically p38-MAPK, was activated by NM.
• p38-MAPK inhibition significantly reduced senescence markers and enhanced cell proliferation.

Conclusions:

• Nitrogen mustard exposure triggers cellular senescence and stress-related MAPK signaling in corneal cells.
• p38-MAPK inhibition demonstrates a protective effect, mitigating senescence and promoting cell recovery.
• Targeting p38-MAPK represents a promising therapeutic strategy for managing NM-induced ocular injury.