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J Sassani, JB Jenkins, PJ McLaughlin, cM Lang, IS Zagon; Corneal Wound Healing In The Diabetic Rat Is Enhanced By Naltrexone - An Opioid Antagonist . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4227.
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Diabetes mellitus (DM) afflicts 16 million persons in the U.S. and many patients are at increased risk for developing corneal disorders such as persistent epithelial defects, recurrent erosions, and delayed wound repair. Blockade of interfacing between the endogenous opioid peptide, opioid growth factor (OGF) and its receptor (OGFr) using the opioid antagonist naltrexone (NTX) enhances the rate of corneal re-epithelialization. Purpose: To test whether delayed corneal wound healing in DM can be compensated by opioid receptor blockade. Method: Adult male rats were rendered diabetic by intravenous injection of streptozotocin (65 mg/kg) to induce hyperglycemia (≷350 mg/dl). At 8 weeks after induction of DM, corneal repair of a 5 mm defect was monitored by light microscopy and quantitative analysis. Results: Diabetic animals healed markedly slower than controls, and had residual defects ranging from 10% (16 hr) to at least 6-fold (48 hr and 56 hr) more than those of non-diabetic rats. Diabetic animals receiving 30 mg/kg NTX twice daily were accelerated in their re-epithelialization relative to DM animals injected with saline. The NTX-exposed DM rats had defects that were 12% (16 hr) to 61% (56 hr) less than diabetic rats injected with saline. Corneas in the NTX-DM animals were re-epithelialized in a manner comparable to nondiabetic rats. The distribution of both OGF and OGFr as determined by immunocytochemistry was similar in diabetic and control animals. Conclusion: These results indicate a delay in re-epithelialization that is dependent on the duration of diabetes, and that intervention of endogenous opioid-receptor interfacing with an opioid antagonist can facilitate the process of wound healing.
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