Efficacy of Osmoprotectants on Prevention and Treatment of Murine 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 by using an intelligently controlled environmental system (ICES). Osmoprotectants betaine, L-carnitine, erythritol, or vehicle (PBS) were topically administered to eyes four 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 until 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-1 beta by using RT-PCR on days 0, 14, 21, and/or 35. RESULTS. Compared with 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 with day 21 (schedule 2). Relative to vehicle, L-carnitine treatment of mouse dry eye for 14 days (days 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 IL1 beta, as well as significantly increased the number of goblet cells. CONCLUSIONS. 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.