Objective: To determine if topical application of naltrexone hydrochloride (NTX), an opioid antagonist, restores tear production and corneal sensation in rats with diabetes mellitus. Methods: Type 1 diabetes was induced with streptozotocin in rats. Tear production was measured by the Schirmer test, and corneal sensitivity, by an esthesiometer. Eye drops of 10-5M NTX or sterile vehicle were administered either once only or 4 times a day for 1 or 5 days; a single drop of insulin (1 U) was given once only. Results: Dry eye and corneal insensitivity were detected in the diabetic rats beginning 5 weeks after streptozotocin injection. One drop of NTX or 4 times a day for 1 or 5 days reestablished tear production and corneal sensitivity within 1 hour of administration. The reversal of dry eye lasted for up to 2 to 3 days depending on drug regimen, but restitution of corneal sensation lasted for 4 to 7 days. Topical application of 1 eye drop of insulin restored corneal sensitivity within 1 hour and lasted for at least 2 days. In contrast, 1 eye drop of insulin did not increase tear production at 1, 24, or 48 hours compared with diabetic animals receiving sterile vehicle. Conclusion: Topical treatment with NTX normalizes tear production and corneal sensitivity in type 1 diabetic rats. Clinical Relevance: Topical application of NTX to the ocular surface may serve as an important strategy for treating dry eye and corneal anesthesia in diabetes. Its effect, if any, in other forms of decreased corneal sensitivity and/or dry eye should be investigated.
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