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Joseph W. Sassani, Anna M. Campbell, Patricia J. McLaughlin, Ian S. Zagon; Topical Naltrexone Reverses Dry Eye in Normal Rats. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3784.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye syndrome is a common condition in aging populations, with an expected incidence of 13% over a 5-year period for persons aged 45 and older. The etiology, pathogenesis, and treatment of dry eye are not completely understood. However, dry eye is often accompanied by superficial punctuate keratopathy that may result in persistent epithelial defect and ulceration. Naltrexone (NTX), an opioid antagonist, has been shown to enhance corneal re-epithelialization in normal rats. The aim of the present study was to determine whether topical application of NTX restores tear production in normal rats with naturally occurring dry eye (i.e., episodic dry eye).
Tear production was measured in male (4-24 weeks) Sprague-Dawley rats by the Schirmer’s test. One drop of 10-5 M NTX in Vigamox, or Vigamox alone, was administered. Rats with Schirmer scores of 6.5 or less were defined as having "dry eye". Corneal sensitivity was measured with an aesthesiometer.
All rats displayed at least one episode of dry eye over the 20 weeks of testing. The mean Schirmer score for rats with dry eye was 5.3 ± 0.1 mm in comparison to a score of 9.1 ± 0.1 mm for animals with normal tear production. Using animals of 9-24 weeks in age, administration of one eye drop of NTX to those rats with dry eye revealed an elevation in Schirmer test scores that was comparable to scores in rats with normal tear production, and this elevation was recorded at 1, 24 and 48 h. At 72 hr, Schirmer test scores for animals with dry eye that received topical NTX returned to baseline values. Animals with dry eye that received topical administration of vehicle did not differ from baseline when tested at 1, 24, 48, or 72 hr. Rats with normal tear production given one drop of NTX or vehicle had Schirmer test scores at 1, 24, 48, or 72 hr that did not deviate from their baseline. Corneal sensitivity of rats with dry eye or normal tear production was comparable.
Topical treatment with NTX normalizes tear production in rats with naturally occurring dry eye. Topical application of NTX to the ocular surface may serve as an important strategy for treating dry eye.
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