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.
