title: Corneal safety of topically applied naltrexone.
abstract: OBJECTIVE
  Naltrexone (NTX), an opioid antagonist, accelerates wound healing of corneal epithelium in normal and diabetic animals. This study examined the safety of NTX by topical application in the cornea.
  
  
  METHODS
  NTX in concentrations of 10(-3), 10(-4), 10(-5), 10(-6), or 10(-7) M was administered topically 4 times/daily for 7 d to the eye of Type 1 diabetic rats (glucose levels >400 mg/dL) (DB), DB animals receiving insulin to maintain normoglycemia (DB-IN), and normal (nondiabetic) (Normal) subjects beginning 8 weeks after onset of diabetes.
  
  
  RESULTS
  No differences in intraocular pressures, corneal thickness, endothelial cell number, or epithelial apoptosis, necrosis, or organization were observed between DB, DB-IN, and Normal groups with and without treatment with NTX. The DB group had a twofold decrease in corneal sensitivity from the Normal and DB-IN groups prior to NTX treatment but were comparable to the Normal and DB-IN groups for at least 2 weeks after chronic exposure to 10(-3) to 10(-7) M NTX was terminated. No differences between Normal and DB-IN groups were noted.
  
  
  CONCLUSIONS
  Topical application of NTX over a 10,000-fold range of dosage had no overt toxicity for the parameters studied, indicating that efficacy studies for the use of NTX in corneal wound healing are warranted.
authors.affiliation: Department of Neural & Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. isz1@psu.edu
authors.forename: Ian S
authors.initials: IS
authors.lastname: Zagon
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Klocek
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Sassani
authors.forename: David T
authors.initials: DT
authors.lastname: Mauger
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: McLaughlin
mesh_terms: D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004728:Endothelium, Corneal / Q000187:drug effects; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects*; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone