PURPOSE: 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.
PURPOSE: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 diabeticrats (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: Ian S Zagon; Matthew S Klocek; James W Griffith; Joseph W Sassani; András M Komáromy; Patricia J McLaughlin Journal: Arch Ophthalmol Date: 2008-04