title: Efficacy of osmoprotectants on prevention and treatment of murine dry eye.
abstract: OBJECTIVE
  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-α, IL-17, IL-6, or IL-1β 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-α 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-α, IL-17, IL-6, or IL-1β, 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.
authors: School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, China.
authors: Wei
authors: W
authors: Chen
authors: Xin
authors: X
authors: Zhang
authors: Jinyang
authors: J
authors: Li
authors: Yu
authors: Y
authors: Wang
authors: Qi
authors: Q
authors: Chen
authors: Chao
authors: C
authors: Hou
authors: Qian
authors: Q
authors: Garrett
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001622:Betaine / Q000008:administration & dosage*; D002331:Carnitine / Q000008:administration & dosage*; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D015352:Dry Eye Syndromes / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004896:Erythritol / Q000008:administration & dosage*; D005260:Female; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D009883:Ophthalmic Solutions; D001622:Betaine; D004896:Erythritol; D002331:Carnitine
keywords: IL-17; IL-1β; IL-6; L-carnitine; TNF-α; animal model; apoptosis; betaine; dry eye; inflammation; osmoprotectants