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J. W. Sassani, M. S. Klocek, P. J. McLaughlin, I. S. Zagon; Topical Treatment With Naltrexone and Insulin Does Not Have an Additive Effect on Accelerating Corneal Epithelial Healing in Type I Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3398. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Patients with diabetes are at increased risk for developing corneal disorders, termed diabetic keratopathy. Treatments for diabetic keratopathy are limited. Preclinical studies have demonstrated that topical administration of either naltrexone (NTX) or insulin (INS) accelerates corneal re-epithelialization in Type I diabetic rats. This study determined the possible additive effect(s) of concomitant topical application of NTX and INS on re-epithelialization of corneal abrasion in hyperglycemic diabetic male Sprague-Dawley rats.
Type 1 diabetes (DB) (glucose levels >400 mg/dl) was induced with streptozotocin; glycemic levels were not controlled with INS. Eight weeks after induction of diabetes, a 5 mm diameter circular abrasion was created in the center of the cornea in one eye of each rat. Eye drops (0.05 ml) of 1U (~ 6 nmol) INS and NTX (10-5 M) in Vigamox (Alcon Laboratories, TX) were given separately 4 times daily for 7 days (NTX/INS); DB control rats received drops of sterile vehicle (DB SV) 4 times daily. Two groups of rats also were given only NTX (DB NTX) or only INS (DB INS). Re-epithelialization was monitored by fluorescein staining, and images were recorded with a CCD camera. Areal measurements were made using Optimas software, and the percentage of epithelial defect over a 40 hr period was calculated.
Concomitant topical application of NTX and INS in diabetic rats did not significantly enhance the corneal healing relative to DB rats treated solely with NTX or INS. Twenty-four hr after formation of an abrasion (~21.7±0.4mm2 area), corneal abrasions in DB rats treated with NTX, INS, or NTX/INS together were significantly smaller (p<0.001) than those in DB SV rats, with reductions ranging from 10 to 34%. The effects on wound healing were not additive. At no time were abrasions of DB NTX/INS rats significantly smaller than abrasions of DB NTX and DB INS rats. Application of NTX and/or INS to the cornea had no effect on blood glucose levels, and it did not affect ocular pressure as measured 2 weeks following debridement.
hese data demonstrate that although NTX or INS accelerate wound healing, concomitant application of NTX and INS to corneal abrasions does not have an additive effect on re-epithelialization.
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