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Updated: Jul 26, 2025
Ex Vivo and In Vivo Animal Models for Mechanical and Chemical Injuries of Corneal Epithelium
Published on: April 6, 2022
Establishing a Dexamethasone Treatment Regimen To Alleviate Sulfur Mustard-Induced Corneal Injuries in a Rabbit
Neha Mishra1, Rama Kant1, Kushal Kandhari1
1Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (N.M., R.K., K.K., N.T.-S., C.A., R.A.) and Department of Ophthalmology, School of Medicine (M.B.P., J.M.P.), University of Colorado-Anschutz Medical Campus, Aurora, Colorado; MRIGlobal, Kansas City, Missouri (P.A., C.R.C.); and Department of Health and Human Services, National Institutes of Health National Eye Institute, Bethesda, Maryland (H.A.).
Dexamethasone (DEX) administered every 8 hours is more effective than every 12 hours in reversing sulfur mustard (SM) ocular injuries. This optimized dosing frequency provides sustained therapeutic benefits for chemical warfare agent exposure.
Area of Science:
- Ophthalmology
- Toxicology
- Pharmacology
Background:
- Sulfur mustard (SM) is a chemical warfare agent causing severe ocular injuries, including inflammation, fibrosis, and neovascularization.
- Current countermeasures for SM-induced ocular toxicity are limited, necessitating the development of effective therapeutic strategies.
- Previous research indicated dexamethasone (DEX) efficacy against nitrogen mustard toxicity with a 2-hour postexposure therapeutic window.
Purpose of the Study:
- To compare the efficacy of two DEX dosing frequencies (every 8 vs. 12 hours) initiated 2 hours post-SM exposure.
- To assess the sustained effects of DEX treatment up to 56 days after SM exposure.
- To establish an optimized DEX treatment regimen for counteracting SM-induced corneal injuries.
Main Methods:
- Corneal clinical assessments (thickness, opacity, ulceration, neovascularization) were conducted at multiple time points post-exposure.
- Histopathological and molecular analyses (H&E staining, COX-2, MMP-9, VEGF, SPARC expression) evaluated corneal injury.
- Statistical analysis using two-way ANOVA with Holm-Sidak post hoc tests determined significance (P < 0.05).
Main Results:
- DEX administration every 8 hours demonstrated greater potency in reversing ocular SM injury compared to every 12 hours.
- The most pronounced therapeutic effects of the 8-hour dosing regimen were observed at 28 and 42 days post-exposure.
- Sustained beneficial effects of DEX treatment were noted up to 56 days after SM exposure, even after cessation of treatment.
Conclusions:
- An 8-hour DEX dosing frequency, initiated 2 hours post-SM exposure, is a superior regimen for mitigating ocular injuries.
- This study provides a comprehensive DEX treatment strategy, including optimal therapeutic window and dosing frequency.
- The findings offer a promising therapeutic approach for managing chemical warfare agent-induced ocular damage.
