Topical insulin enhances corneal repair in Type 1 diabetic rats

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 streptozo...

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Published in:The FASEB journal 2007, Vol.21 (6), p.A1200-A1200
Main Authors: Zagon, Ian S., Sassani, Joseph W., McLaughlin, Patricia J., Klocek, Matthew S.
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Sassani, Joseph W.
McLaughlin, Patricia J.
Klocek, Matthew S.
description 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 (
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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 &gt;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 (&lt;0.05). At 24 hr and 32 hr following abrasion, the wounds in DB‐IN rats were 37% and 53% smaller (p&lt;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&lt;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. 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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 (&lt;0.05). At 24 hr and 32 hr following abrasion, the wounds in DB‐IN rats were 37% and 53% smaller (p&lt;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&lt;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. 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