title: Resolvin E1 (RX-10001) reduces corneal epithelial barrier disruption and protects against goblet cell loss in a murine model of dry eye.
abstract: OBJECTIVE
  Resolvin E1 (RvE1; RX-10001) belongs to a new class of endogenous immunoregulating mediators, originally identified as a metabolite of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid. Based on its proven efficacy in models of chronic inflammation, this study investigated the efficacy of resolvin E1 in a murine model of dry eye.
  
  
  METHODS
  C57/B6 mice, aged 6 to 8 weeks, were treated with systemic scopolamine and exposed to air draft and low humidity for 16 hours/day for 5 days and allocated to the following groups: unexposed controls, disease controls, treatment with vehicle or RvE1 delivered topically as its methyl ester prodrug, RX-10005, to enhance corneal surface penetration. Treatment was initiated at the time of desiccating stress induction. Treatment efficacy was assessed by corneal permeability using Oregon Green Dextran and by conjunctival goblet cell density using periodic acid-Schiff reagent.
  
  
  RESULTS
  RvE1 reduced the increase in corneal staining by 80% compared with untreated disease controls. Goblet cell density was reduced by 20% in disease controls but fully maintained in the group receiving RvE1.
  
  
  CONCLUSIONS
  RvE1, delivered as its methyl ester prodrug, improved the outcome measures of corneal staining and goblet cell density in this murine model of dry eye, indicating the potential utility of endogenous resolvins and resolvin analogues in the treatment of dry eye.
authors.affiliation: Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Cintia S
authors.initials: CS
authors.lastname: de Paiva
authors.forename: C Eric
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Per
authors.initials: P
authors.lastname: Gjörstrup
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001692:Biological Transport; D002452:Cell Count; D002463:Cell Membrane Permeability / Q000502:physiology; D002470:Cell Survival; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000378:metabolism / Q000517:prevention & control*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D020397:Goblet Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011355:Prodrugs / Q000494:pharmacology*
chemical_list: D005456:Fluorescent Dyes; D011355:Prodrugs; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid