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M. Hornof, S. Goyal, R. Dana; Thiolated Chitosan for the Treatment of Dry Eye - Evaluation in Mice Using the Controlled-Environment Chamber Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3663.
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The role of a new topically applied thiolated polymer - chitosan-N-acetylcysteine conjugate (chitosan-NAC) - was investigated in a mouse model of dry eye disease. It is postulated that interaction between thiol groups of the chitosan-NAC with cysteine-rich mucin (MUC5AC) increases residence time of the polymer on the ocular surface and tear film stability.
Dry eye was induced by placing female C57BL/6 mice in a controlled-environment chamber (relative humidity below 30%, continuous airflow 15l/min) and aggravated by application of atropine and scopolamine. Fluorescein staining was used to monitor the effect of desiccating stress on the corneal surface during the study. Three topical formulations (chitosan-NAC 0.5%, chitosan-NAC 0.3% and Artelac® EDO® artificial tear containing 0.32% methylhydroxypropylcellulose as positive control) were applied in a masked fashion twice a day for 2 weeks starting 48h after induction of dry eye. An untreated dry eye group served as control. Quantitative Real-Time PCR was performed at the end of the study to evaluate TNF-, IL-1 and IL-1β expression in ocular surface tissues.
Mice treated with chitosan-NAC 0.3% showed a downward trend in corneal staining compared to the other 3 groups, which was not statistically significant. Treatment with chitosan-NAC 0.3% resulted in a significantly decreased expression of TNF- in the conjunctiva. This effect was not observed in the cornea, where only the positive control significantly decreased both TNF- and IL-1 expression.
Evaluation of important molecular biomarkers of dry eye disease such as TNF- suggests that chitosan-NAC may have some protective ocular surface properties. However, clinical data as reflected by corneal fluorescein scores did not indicate statistically significant improvement of tear film stability in any of the groups tested. Future work will focus on the use of chitosan-NAC in the prevention of ocular surface damage.
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