{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:56:06Z","timestamp":1790081766990,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,7,29]],"date-time":"2013-07-29T00:00:00Z","timestamp":1375056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ocular surface complications of type 2 diabetes are associated with reductions in tear production, increased corneal surface sensitivity, and delayed corneal re\u2010epithelialization. This study examined the efficacy of topical application of the opioid antagonist naltrexone (<jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content>) in reversing these diabetic\u2010related ocular surface complications in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The genetic <jats:italic>db\/db<\/jats:italic> mouse model of type 2 diabetes, along with <jats:styled-content style=\"fixed-case\">C57Bl<\/jats:styled-content>\/6 wild\u2010type 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<jats:sup>\u22125<\/jats:sup>\u2009<jats:styled-content style=\"fixed-case\">M NTX<\/jats:styled-content> in sterile <jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>igamox (Vigamox, Alcon Laboratories, Fort Worth, Texas, USA) or sterile <jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>igamox alone, and tear production, corneal sensitivity, and reepithelialization were monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In comparison to diabetic mice receiving vehicle only, <jats:italic>db\/db<\/jats:italic> mice treated with one drop of <jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content> demonstrated a marked reversal in dry eye and ocular surface hypersensitivity within 1\u2009h of one drop of <jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content>. Reversal of the complications in <jats:italic>db\/db<\/jats:italic> mice usually lasted for 48\u201390\u2009h. Corneal epithelial repair in <jats:italic>db\/db<\/jats:italic> mice was enhanced following a regimen of three drops of <jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content> daily such that by 72\u2009h, residual wounds were one third the size in <jats:italic>db\/db<\/jats:italic> mice receiving <jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content> relative to diabetic mice receiving vehicle. Application of <jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>igamox alone had no effect. No adverse effects of <jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content> administration were noted in the cornea.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first report of the efficacy of topical <jats:styled-content style=\"fixed-case\">NTX<\/jats:styled-content> in reversing corneal surface complications in type 2 diabetic mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.12144","type":"journal-article","created":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T11:55:13Z","timestamp":1371556513000},"page":"159-168","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Ocular surface abnormalities related to type 2 diabetes are reversed by the opioid antagonist naltrexone"],"prefix":"10.1111","volume":"42","author":[{"given":"Ian S","family":"Zagon","sequence":"first","affiliation":[{"name":"Department of Neural and Behavioral Science The Pennsylvania State University College of Medicine  Hershey Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph W","family":"Sassani","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Pathology The Pennsylvania State University College of Medicine  Hershey Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A","family":"Immonen","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Science The Pennsylvania State University College of Medicine  Hershey Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Science The Pennsylvania State University College of Medicine  Hershey Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,29]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"American Diabetes Association.2013. 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