Ocular surface abnormalities related to type 2 diabetes are reversed by the opioid antagonist naltrexone

Background: Ocular surface complications of type 2 diabetes are associated with reductions in tear production, increased corneal surface sensitivity, and delayed corneal re-epithelialization. This study examined the efficacy of topical application of the opioid antagonist naltrexone (NTX) in reversing these diabetic-related ocular surface complications in mice. Methods: The genetic db/db mouse model of type 2 diabetes, along with C57Bl/6 wild-type mice were investigated. Tear production was assessed by phenol red impregnated threads, and ocular surface sensitivity was measured using Von Frey filaments. Centrally located, circular corneal abrasions were created in mice and residual epithelial defects measured by fluorescein photography. Animals in each group received topical applications of drops of 10^-5M NTX in sterile Vigamox (Vigamox, Alcon Laboratories, Fort Worth, Texas, USA) or sterile Vigamox alone, and tear production, corneal sensitivity, and reepithelialization were monitored. Results: In comparison to diabetic mice receiving vehicle only, db/db mice treated with one drop of NTX demonstrated a marked reversal in dry eye and ocular surface hypersensitivity within 1h of one drop of NTX. Reversal of the complications in db/db mice usually lasted for 48-90h. Corneal epithelial repair in db/db mice was enhanced following a regimen of three drops of NTX daily such that by 72h, residual wounds were one third the size in db/db mice receiving NTX relative to diabetic mice receiving vehicle. Application of Vigamox alone had no effect. No adverse effects of NTX administration were noted in the cornea. Conclusions: This is the first report of the efficacy of topical NTX in reversing corneal surface complications in type 2 diabetic mice.