MUSTARD GAS EXPOSURE IMPAIRS VISION VIA ALTERATIONS IN CORNEAL STROMAL ARCHITECTURE AND FIBROTIC GENES IN VIVO

Abstract

Purpose : Sulfur mustard gas (SM), a chemical weapon, has been used in many wars and most recently in Syrian conflict. SM exposure to disrupts the corneal stroma that constitutes 90% of the cornea. The characteristic collagen fibrils arrangement is necessary for corneal transparency and clear vision. This study evaluated changes in stromal collagen fibrils arrangement in post SM in rabbit eyes with transmission electron microscopy (TEM) and its impact on vision in live rabbits with 2D and 3D clinical eye imaging.

Methods : Fifty-four New Zealand White Rabbits divided into three groups (Naïve, Vehicle, SM-Vapor) were exposed to SM. At day-3, day-7, and day-14, eyes were examined/imaged in vivo with stereomicroscopy, slit-lamp, optical coherence tomography and confocal microscopes. Post euthanasia, H&E and Picrosirius Red staining to determine stromal integrity and collagen levels and TEM analysis were conducted at 50,000x to quantify collagen size and distance.

Results : Clinical eye exams of SM exposed rabbit eyes demonstrated significantly increased corneal haze (p<0.0001), thickness (p<0.0001), and debris (p<0.1) in stroma and significantly reduced stromal cell density (p<0.0001) compared to naïve corneas at all tested timepoints. TEM showed significantly altered arrangement of collagen fibrils in stroma of SM-exposed eyes at tested times (p<0.0001 or p<0.001). H&E and Picrosirius Red staining supported clinical findings with notable damage to the corneal epithelial stromal barrier at tested times.

Conclusions : Acute vision loss from mustard gas occurs via alterations in characteristic collagen fibrils arrangement in corneal stroma and changes in key fibrotic markers, TGFb and collagens.

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