Topical application of betaine limited progression of environmentally induced dry eye

Purpose: To evaluate the efficacy of osmoprotectants on prevention and treatment of dry eye in a murine model. Methods: Dry eye was induced in mice using an intelligently controlled environmental system (ICES). Osmoprotectants betaine, L-carnitine, erythritol, or vehicle (PBS) were topically administered to eyes 4 times daily following two schedules: Schedule 1 (modeling prevention): dosing started at the beginning of housing in ICES and lasted for 21 or 35 days; Schedule 2 (modeling treatment): dosing started after ICES-housed mice developed dry eye (Day 21), continuing till Day 35. Treatment efficacy was evaluated for corneal fluorescein staining; corneal epithelial apoptosis by TUNEL and caspase-3 assays; goblet cell numbers by PAS staining; and expression of inflammatory mediators, TNF-alpha, IL-17, IL-6 or IL-1beta using RT-PCR on Days 0, 14, 21 and/or 35.
Results: Compared to vehicle, prophylactic administration of betaine, L-carnitine or erythritol significantly decreased corneal staining and expression of TNF-alpha and IL-17 on Day 21 (Schedule 1). Treatment of mouse dry eye with osmoprotectants significantly reduced corneal staining on Day 35 compared to Day 21 (Schedule 2). Relative to vehicle, L-carnitine treatment of mouse dry eye for 14 days (Day 21 to 35) resulted in a significant reduction in corneal staining, number of TUNEL-positive cells, and expression of TNF-alpha, IL-17, IL-6, or IL-1beta, as well significantly increased number of goblet cells.
Conclusion: Topical application of betaine, L-carnitine or erythritol systematically limited progression of environmentally induced dry eye. L-carnitine can also reduce the severity of such dry eye conditions.

Chen, W., et al., Efficacy of Osmoprotectants on Prevention and Treatment of Murine Dry Eye. Invest Ophthalmol Vis Sci, 2013