Comparative Evaluation of Cigarette Smoke and a Heated Tobacco Product on Corneal Oxidative Stress in an Air/Liquid Interface Model

Purpose: Tobacco smoke harbors toxic combustion by-products contributing to inflammatory diseases. Cigarette smoke's impact on ocular diseases has been poorly characterized, despite conjunctival mucosa's sensitivity to these toxicants. Of note, cigarette smoke triggers redness, tearing, and discomfort, accounting as a risk factor for glaucoma, macular degeneration, cataracts, and other eye conditions. Low quit rates of cessation highlight the need for alternatives. Heated tobacco products (HTPs), may represent a less toxic alternative for those smokers. This study evaluates cigarette smoke and HTPs effects on cornea under standard and clinically relevant conditions. Methods: Corneal tissues collected from donors and in vitro model in two different cell lines of corneal epithelium were exposed to cigarette (1R6F) smoke and HTPs vapor. Air exposure was included as a control. Tissue pathological evaluation was carried out by hematoxylin and eosin staining. Reactive oxygen species (ROS) were measured, and quantitative PCR assessed inflammatory and antioxidant genes expression. Proteome analysis was used to evaluate differentially expressed proteins related to the oxidative stress. Scratch assay measured smoke and HTPs impact on cells. Results: Hematoxylin & eosin staining highlighted that cigarette smoke impairs corneal tissue integrity, leading to ROS accumulation and inflammation, as proved by qPCR analysis. Proteomic analysis showed that corneal tissue's proteins were differently oxidized by the different experimental conditions. HTP targeted structural intracellular proteins, whereas 1R6F affects different members of collagen family. Finally, cigarette smoke, but not HTPs, impairs epithelial cells wound closure. Conclusions: Smoking increases oxidative stress, leading to significant corneal damage and inflammation. HTPs may offer a less toxic alternative.