Abstract
Purpose: :
The role of a topically applied thiolated polymer, chitosan-N-acetylcysteine conjugate (C-NAC), was investigated in a dry eye mouse model. It is postulated that interaction between thiol groups of the C-NAC with cysteine-rich mucins (MUC5AC) increases tear film stability.
Methods: :
Dry eye was induced by injecting botulinum toxin B (BTX-B) in the right eye lacrimal glands of CBA/J mice. Eye drops containing C-NAC 0.5%, C-NAC 0.3%, vehicle (control), artificial tear (Artelac® EDO®) or fluorometholone (FML®) were applied in a masked fashion to group A-E, respectively, twice per day starting from day 3 until 4 weeks after BTX-B injection. Corneal fluorescein staining was periodically recorded. Quantitative Real-Time RT-PCR and immunofluorescence staining were performed at the end of the study to evaluate expression of inflammatory cytokines in ocular surface tissues.
Results: :
Mice treated with C-NAC 0.5% and fluorometholone showed a downward trend in corneal staining compared to the other 3 groups, which was not statistically significant. C-NAC formulations, fluorometholone and artificial tear significantly decreased IL-1β, IL-10, IL-12, and TNF- expression in ocular surface tissues in comparison to the control (Tab. 1).
Conclusions: :
This study has demonstrated the potential usefulness of the BTX-B-induced dry eye mouse model to evaluate new dry eye treatment strategies. Evaluation of important molecular biomarkers of dry eye disease suggests that C-NAC may have some protective ocular surface properties. However, clinical data did not indicate statistically significant improvement of tear film stability in any of the groups tested.
Keywords: cornea: tears/tear film/dry eye • cytokines/chemokines • inflammation