Abstract
Purpose::
Patients with diabetes are at increased risk for developing corneal disorders, termed diabetic keratopathy. Treatments for diabetic keratopathy are limited. This study determined the effect(s) of topical application of insulin on re-epithelialization of corneal abrasions in hyperglycemic diabetic male Sprague-Dawley rats.
Methods::
Type 1 diabetes (DB) (glucose levels >400 mg/dl) was induced with streptozotocin; glycemic levels were not controlled with insulin. 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), 2U, or 5U insulin dissolved in Vigamox (Alcon Laboratories, TX) were given 4 times daily for 7 days; DB control rats received only 4 drops of vehicle daily. Wound healing 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.
Results::
Topical insulin application in diabetic rats significantly enhanced the corneal healing relative to DB rats receiving only vehicle. Twenty-four hr after formation of an abrasion (~22.2±0.8 mm2 area), corneal wounds in DB rats treated with either 1U, 2U, or 5U of insulin were significantly smaller (p<0.05) than those in DB rats receiving only vehicle, with reductions up to 37% recorded. The effects on wound healing were not dose dependent. At 24 and 32 hr following abrasion, corneal wounds in rats receiving topical insulin were up to 37% and 53%, respectively, smaller (p<0.001) than residual wounds in DB rats receiving vehicle. Application of insulin to the cornea had no effect on blood glucose levels, and it did not affect ocular pressure as measured prior to or 2 weeks following debridement. Topical insulin had no effect on corneal re-epithelialization of non-diabetic rats.
Conclusions::
These data demonstrate that direct application of insulin to corneal wounds enhances re-epithelialization without influencing ocular pressure or systemic glucose levels in uncontrolled diabetic rats.
Keywords: cornea: epithelium • wound healing • diabetes