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Ratnakar Tripathi, Nishant Rajiv Sinha, Praveen Kumar Balne, Alexandria Hofmann, Sydney L. Green, Laila A Suleaiman, Prashant Sinha, Nathan P Hesemann, Shyam S Chaurasia, Rajiv R Mohan; Evaluation of delayed/chronic corneal toxicity and clinical manifestations for 4-month after mustard gas exposure to rabbit eyes in vivo. Invest. Ophthalmol. Vis. Sci. 2022;63(7):115 – A0213.
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© ARVO (1962-2015); The Authors (2016-present)
Sulfur mustard (SM) gas exposure to the eye causes severe toxicity to the cornea called mustard gas keratopathy (MGK). This study investigated delayed/chronic corneal toxicity and clinical manifestations at 1-, 2-, and 4-months in rabbit eyes in vivo exposed to SM.
The study was approved by the institutional animal care and use committee and followed ARVO guidelines. New Zealand White rabbits (n = 36) were exposed to SM vapor at a target concentration of 200 mg-min/m3 for 8 minutes. Clinical eye manifestations in live rabbits were performed with the slit-lamp microscope, confocal HRT3 microscope, Fante's grading system, fluorescein staining, Schirmer’s tests, pachymetry, applanation tonometry, and optical coherence tomography. At the endpoints, rabbits were humanely euthanized, and corneas were collected for histological, molecular, and cellular analyses.
SM exposed rabbit corneas showed a significant corneal haze (Fante’s scores 2-4; p<0.0001), central corneal thickness (749-560 ± 40.7; p<0.0001), tear flow (18-21± 2.3 p<0.0001), and corneal edema, decreased in keratocyte density, loss of endothelium cell number and corneal neovascularization (NV) compared to naïve untreated control corneas up to 2-month post-SM exposure. At 4-month post-SM exposure, rabbit corneas developed additional pathologies including severe ulcer of varying sizes, epithelial defects, and NV at the peri-limbal plexus regions. Also, few of the SM-exposed rabbit eyes showed ruptured cornea with iris plugged the hole and prolapsed. In these rabbits, significantly decreased central corneal thickness (p<0.001) and severe epithelium-erosion were observed. The clinical quantitative analyses matched typical delayed/chronic corneal pathology. Histological and molecular studies are underway.
Mustard gas exposure to eyes cause severe delayed/chronic corneal toxicity in rabbits in vivo. Additional analysis is warranted.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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