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Ian S. Zagon, Joseph W. Sassani, Jessica A. Immonen, Patricia J. McLaughlin; Topical Naltrexone Reverses Dry Eye in Mice with Type 2 Diabetes (db/db). Invest. Ophthalmol. Vis. Sci. 2011;52(14):3779.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye is a chronic complication of Type 2 diabetes that manifests with punctuate keratopathy, ulcerations, and persistent epithelial defects. The prevalence of dry eye associated with Type 2 diabetes has been estimated at more than 50%, with advancing age and female gender increasing the incidence. The etiology, pathogenesis, and treatment of this condition in Type 2 diabetes are unclear. In this study, homozygous genetic mice (B6.Cg-m+/+Leprdb/J, db/db), a model for Type 2 diabetes, and C57Bl/6 wildtype littermates (WT) were utilized to study tear production.
Male db/db mice weighing ~45 g with blood glucose levels >250 mg/dl and WT mice weighing ~22 g with glucose levels of ~140 mg/dl were monitored for tear production using threads [Zone Quick, Menicon America, San Mateo, CA]. Following the establishment of baseline values, one drop of the opioid antagonist, naltrexone (NTX), dissolved in Sorenson’s phosphate buffer (SPB) was applied topically to the cornea. Some db/db or WT mice received one drop of SPB as controls. Tear production was measured 1, 24, 48, 72, and 90 hr after the first drop of NTX. Measurements were conducted without anesthesia.
Baseline tear production for db/db mice (3.4±0.5 mm) was 36% of values for WT mice (9.4±0.7 mm); this was considered to be dry eye. Following 1 drop of NTX to db/db mice, scores were 2.5-fold greater than baseline within 1 hr, and rose to 3.5-fold for 24 and 48 hr. At 72 and 90 hr, the values for db/db receiving NTX were comparable to baseline. Topical NTX did not alter scores for tear production baseline in WT mice. Mice receiving vehicle alone had no affect on tear production in db/db mice or WT mice.
These data indicate that as little as one drop of NTX reverses dry eye syndrome for up to 72 hr in Type 2 diabetic mice, and supports NTX as a novel therapeutic approach for treatment of corneal complications from diabetic dry eye.
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