Assessment of insulin-degrading enzyme inhibitor for the treatment of corneal erosion in a rat model.

Abstract

BACKGROUND: Diabetes poses a risk to diabetic keratopathy in up to two-thirds of patients. Insulin-degrading enzyme (IDE) is a protease that can break down insulin and several growth factors and may impair wound healing. Increased IDE levels have been found in fluid from diabetic skin ulcers. This study sought to determine the effect of IDE inhibitor on corneal wound healing in a rat model. METHODS: Thirty-four male Wistar rats were divided into two groups: no diabetes and streptozocin-induced diabetes. Six weeks later, a 4-mm central corneal erosion was created under anesthesia in the right eye of all rats. In each group, half the rats were treated with ADT21 drops (IDE inhibitor) and half with NaCl 0.9% (sham) drops, four times daily. Image J analysis was performed to evaluate the area of erosion and healing rate. RESULTS: There was a trend for more rapid healing in rats treated with IDEI than NaCl drops, regardless of the diabetic condition. Comparison of erosion closure over time revealed that the wounds closed significantly more quickly in the non-diabetic rats treated with IDEI than in the non-diabetic rats treated with NaCl (p = 0.045), overall mean closure time 56.00 h, 95% CI [50.54, 61.46]. No such difference was seen in the diabetic group. CONCLUSIONS: To our knowledge, this is the first study to test ADT21 drops as a novel treatment for corneal wound repair. Our results suggest a potential benefit of IDE inhibitor for treating corneal injury.