Effects of Menthol-Containing Artificial Tears on Tear Stimulation and Ocular Surface Integrity in Normal and Dry Eye Rat Models

ABSTRACT

Purpose: To evaluate the effects of menthol-containing artificial tears on tear stimulation and ocular surface integrity in normal and dry eye rat models.

Methods: A total of 54 male Lewis rats were used. The levels of tear secretion and tear MUC5AC concentrations were compared between the menthol-containing artificial tear-treated group (menthol group) and the vehicle-treated group (vehicle group). The groups were compared after a single instillation to evaluate the immediate effects, and after repeated instillation (five times a day for 5 days) to evaluate the longer-term effects. Tear lactate dehydrogenase (LDH) activity was measured to evaluate eye drop instillation-induced ocular surface damage. The effects of menthol-containing artificial tears were also evaluated in a dry eye rat model.

Results: After a single instillation of menthol-containing artificial tears, tear secretion increased from 4.37 (±0.75) mm at baseline to 7.37 (±1.60) mm. However, after repeated instillations, the effects of tear stimulation decreased. The tear MUC5AC concentration was significantly lower in the menthol group than in the vehicle group after a single instillation, but not after repeated instillation. However, the tear LDH concentration was significantly increased in the menthol group after repeated instillation. In the dry eye rat model, the extent of menthol-induced tear stimulation was reduced.

Conclusions: Menthol-containing artificial tears increased tear secretion, but lowered the tear MUC5AC concentration. Menthol-induced tear stimulation was reduced after repeated instillation for 5 days and in the dry eye rat model. Conversely, repeated instillation of menthol-induced ocular surface damage, resulting in increased tear LDH activity.

KEYWORDS:

• Menthol
• dry eye
• tear stimulation
• transient receptor potential melastatin-8

Acknowledgments

Author contributions: Study design (A.S.M., S.J.S.); study conduct (A.S.M., S.J.S.); data collection (A.S.M., K.B.R.); data analysis and interpretation (A.S.M., S.J.S., K.B.R.); and manuscript preparation, review, and approval (A.S.M., S.J.S., K.B.R., E.Y.S., K.H.M., H.K.L).

Conflict of Interest

The authors have no proprietary or commercial interest in any concept or product discussed in this article.

Additional information

Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the 6 S. AHN ET AL. Ministry of Education (NRF-2017R1D1A1B03028552). The funding organization had no role in the design or conduct of this research.