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Qian Garrett, Xin Zhang, Yu Wang, Peter Simmons, Joseph Vehige, Jinyang Li, Wei Chen; Topical administration of L-carnitine on prevention and treatment of murine dry eye. Invest. Ophthalmol. Vis. Sci. 2013;54(15):921.
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L-carnitine has been reported to help maintain human corneal epithelial cell volume under hyperosmotic stress and ameliorate aspects of hyperosmotic stress-induced apoptosis. Eye drops containing L-carnitine have been shown to produce rapid and consistent improvements in the signs and symptoms of dry eye. Using a murine dry eye model, the present study evaluated the efficacy of L-carnitine on prevention and treatment of dry eye.
Dry eye was induced in mice using an intelligently controlled environmental system (ICES). L-carnitine (in PBS) or PBS alone was topically administered to the mouse eyes 4 times daily according to two schedules: Schedule 1 (S1): to model prevention, dosing started at the beginning of housing in ICES (Day1) and lasted for 21 days; Schedule 2 (S2): to model treatment, dosing started on Day22 after the housed mice developed dry eye and lasted until Day35. The efficacy of the L-carnitine treatment compared to that of the vehicle (PBS) was tested for ocular surface integrity by fluorescein staining; corneal epithelial apoptosis by TUNEL or Caspase-3 assays; goblet cell numbers by PAS staining; and expression of inflammatory mediators, TNF-α, IL-17, IL-6 or IL-1β using real-time PCR, on Days 0, 14, 21 and/or 35.
Compared to the vehicle, eyes treated with L-carnitine showed a significant reduction in corneal fluorescein staining on Day 14, 21 and 35 for S1 (p=0.0001, 0.0001, and 0.017, respectively) and Day35 for S2 (p=0.0001); the number of TUNEL-positive apoptotic corneal epithelial cells on Day21 for S1 (p=0.032) or Day35 for S2 (p=0.005); the expression level of TNF-α, IL-17, IL-6, or IL-1β (all p<0.05); and visible reduction in corneal epithelial expression of caspase-3; as well as a significant increase in goblet cell density for both schedules (p=0.003 and 0.0001 on Day21 for S1 and Day35 for S2, respectively).
Topical application of L-carnitine could limit progression as well as reduce the severity of dry eye, suggesting L-carnitine has prophylactic and therapeutic potential in dry eye management and treatment.
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