Issac Levy, Dolev Dollberg, Irit Bahar, Assaf Dotan, Levy Issac
Department of Ophthalmology and Laboratory of Eye Research, Rabin Medical Center - Beilinson Hospital, Felsenstein Medical Research Center , 39 Jabotinski St., Petach Tikva, 49100, Israel.
Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Graefes Arch Clin Exp Ophthalmol. 2025 Apr;263(4):1015-1021. doi: 10.1007/s00417-024-06717-1. Epub 2024 Dec 23.
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.
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.
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.
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.
糖尿病在多达三分之二的患者中会引发糖尿病性角膜病变风险。胰岛素降解酶(IDE)是一种蛋白酶,可分解胰岛素和多种生长因子,并可能损害伤口愈合。在糖尿病皮肤溃疡的渗出液中已发现IDE水平升高。本研究旨在确定IDE抑制剂对大鼠模型角膜伤口愈合的影响。
将34只雄性Wistar大鼠分为两组:非糖尿病组和链脲佐菌素诱导的糖尿病组。六周后,在所有大鼠的右眼麻醉下制作一个4毫米的中央角膜糜烂。在每组中,一半的大鼠用ADT21滴眼液(IDE抑制剂)治疗,另一半用0.9%氯化钠(假手术)滴眼液治疗,每日四次。使用Image J分析来评估糜烂面积和愈合率。
无论糖尿病状况如何,用IDEI治疗的大鼠比用氯化钠滴眼液治疗的大鼠有更快愈合的趋势。对糜烂闭合随时间的比较显示,用IDEI治疗的非糖尿病大鼠的伤口闭合明显比用氯化钠治疗的非糖尿病大鼠更快(p = 0.045),总体平均闭合时间为56.00小时,95%置信区间[50.54, 61.46]。糖尿病组未观察到这种差异。
据我们所知,这是第一项测试ADT21滴眼液作为角膜伤口修复新疗法的研究。我们的结果表明IDE抑制剂在治疗角膜损伤方面具有潜在益处。