Premium
The Opioid Antagonist Naltrexone Reverses Dry Eye and Enhances Corneal Wound Healing in Type II (db/db) Mice
Author(s) -
Zagon Ian S.,
Sassani Joseph W.,
Immonen Jessica A.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1095.7
Subject(s) - medicine , cornea , corneal abrasion , naltrexone , ophthalmology , type 2 diabetes , abrasion (mechanical) , wound healing , endocrinology , antagonist , diabetes mellitus , surgery , receptor , mechanical engineering , engineering
Complications of type II diabetes include delayed re‐epithelialization of the cornea and dry eye. The etiology, pathogenesis, and treatment of these conditions are unclear. In this study, homozygous genetic mice (B6.Cg‐m+/+Leprdb/J, db/db), a model for Type II diabetes, and C57BL/6 wildtype (WT) animals, were utilized to study the rates of corneal wound closure and tear production. Db/db and WT mice weighed 45g and 25g, respectively, and the db/db animals had blood glucose levels of 250–400 mg/dl. Central corneal abrasions were treated 3x/day with 10‐5 M naltrexone (NTX) dissolved in Vigamox. At 72 hr, the residual corneal abrasion in db/db mice receiving vehicle was 14.7±4.3 mm2 in comparison to 9.2±2.5 mm2 for db/db mice receiving NTX. WT mice receiving vehicle or NTX had corneal wounds of 8.4±2.1 mm2 and 4.9±1.5 mm2. Baseline Schirmer scores for db/db mice measured 3–4 mm indicating dry eye; following 1 drop of NTX scores averaged 8.8±0.5 mm (p<0.05). Normal tear production in db/db mice was evident for 72 hr, but returned to a dry eye condition at 90 hr. Vehicle alone had no affect on tear production in db/db mice or WT mice, and NTX did not alter normal eyes with Schirmer scores ranging from 6–11 mm. These data indicate that NTX reverses corneal complications in Type II diabetic mice, and supports novel therapeutic approaches for treatment of corneal complications. Supported by ARRA award NIH/NEI EY016666‐04S1.