Decoding ozone's impact on the cornea: disruption of barrier integrity and its molecular drivers

Area of Science:

• Ophthalmology
• Environmental Health
• Toxicology

Background:

• Ozone is a significant air pollutant with known adverse health effects.
• Ozone's impact on ocular tissues, particularly the cornea, requires further investigation to understand cellular and molecular responses.

Purpose of the Study:

• To investigate the effects of ozone exposure on mouse corneas and human corneal epithelial cells (HCEC).
• To elucidate the molecular mechanisms underlying ozone-induced corneal toxicity, focusing on inflammation and nitrative stress.

Main Methods:

• Exposure of mouse corneas and HCECs to cyclic ozone.
• Assessment of corneal structure, epithelial barrier function, cell viability, and inflammatory markers.
• Analysis of nitrative stress markers (3-nitrotyrosine) and inflammasome components (NLRP3, caspase-1, GSDMD).
• Evaluation of therapeutic intervention using an anti-nitration agent (MnTMPyP).

Main Results:

• Ozone exposure caused corneal stromal thinning, increased epithelial thickness, and impaired barrier function.
• Significant inflammatory cell infiltration and elevated 3-nitrotyrosine levels were observed in mouse corneas.
• HCECs showed reduced viability, increased nitrative stress, and activation of the NLRP3/caspase-1/GSDMD pathway.
• MnTMPyP treatment mitigated ozone-induced nitrative stress and pyroptosis in HCECs.

Conclusions:

• Ozone exposure induces corneal toxicity through nitrative stress and NLRP3 inflammasome-mediated pyroptosis.
• These findings highlight the detrimental effects of ozone on corneal health.
• Targeting nitrative stress and inflammasome activation may offer therapeutic strategies against ozone-related corneal damage.