Effect of chitosan-N-acetylcysteine conjugate in a mouse model of botulinum toxin B-induced dry eye

Objective: To evaluate the effect of a thiolated polymer lubricant, chitosan-N-acetylcysteine conjugate (C- NAC), in a mouse model of dry eye. Methods: Eye drops containing 0.5% C-NAC, 0.3% C- NAC, a vehicle (control group), artificial tears, or fluo- rometholone were applied in a masked fashion in a mouse model of induced dry eye from 3 days to 4 weeks after botulinum toxin B injection. Corneal fluorescein staining was periodically recorded. Real-time reverse tran- scriptase-polymerase chain reaction and immunofluo- rescence staining were performed at the end of the study to evaluate inflammatory cytokine expressions. Results: Mice treated with C-NAC, 0.5%, and fluoro- metholone showed a downward trend that was not statistically significant in corneal staining compared with the other groups. Chitosan-NAC formulations, fluoro-metholone, and artificial tears significantly decreased IL-1β (interleukin 1β), IL-10, IL-12α, and tumor necrosis factor a expression in ocular surface tissues. Conclusions: The botulinum toxin B-induced dry eye mouse model is potentially useful in evaluating new dry eye treatment. Evaluation of important molecular bio- markers suggests that C-NAC may impart some protective ocular surface properties. However, clinical data did not indicate statistically significant improvement of tear production and corneal staining in any of the groups tested. Clinical Relevance: Topically applied C-NAC might protect the ocular surface in dry eye syndrome, as evidenced by decreased inflammatory cytokine expression.