Topical insulin enhances corneal repair in Type 1 diabetic rats

Abstract

Complications of Type 1 diabetes include diabetic keratopathy. To determine whether topical application of insulin restores delays in re-epithelialization of central corneal wounds in rats with uncontrolled hyperglycemia, Type 1 diabetes (DB) (glucose levels >400 mg/dl) was induced with streptozotocin. Eight weeks after onset of diabetes, a 5 mm central corneal wound was created in one eye/rat. Eye drops containing 1U insulin (Humulin R) dissolved in Vigamox were given 4 times daily for 7 days (= DB-IN). Other DB rats received 4 drops of vehicle daily. Wound healing was monitored by fluorescein dye; 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. Topical insulin had no effect on corneal re-epithelialization of non-diabetic rats. However, the DB-IN group had significantly enhanced corneal healing relative to DB rats. Beginning 16 hr following formation of an abrasion (22.2 ± 0.8 mm2 area), DB rats had 77% residual wounds relative to 61% in DB-IN rats (<0.05). At 24 hr and 32 hr following abrasion, the wounds in DB-IN rats were 37% and 53% smaller (p<0.001) than those in DB rats, respectively. At 40 hr, with less than 20% residual wound in DB rats, there was a 61% smaller wound in DB-IN rats relative to these DB animals (p<0.05). Topical insulin had no effect on blood glucose levels, or on ocular pressure as measured prior to or 2 weeks following debridement. These data are the first to demonstrate that topical application of insulin enhances corneal wound healing in diabetes. Supported by NIH Grant EY16666.