Department of Neural & Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Brain Res Bull. 2010 Feb 15;81(2-3):248-55. doi: 10.1016/j.brainresbull.2009.10.009. Epub 2009 Oct 21.
Delayed corneal reepithelialization is a complication of diabetes, and may lead to ulcers and erosions, which cause ocular morbidity and visual loss. This study examined the efficacy of naltrexone (NTX), a long-acting, potent opioid antagonist, applied topically, to facilitate the repair of standardized corneal abrasions in diabetic (alloxan-induced) New Zealand White rabbits (glucose levels>450 mg/dL). NTX at a concentration of 10(-4)M, or sterile vehicle (SV), was administered topically 4 times per day for 7 days to the abraded eye of uncontrolled Type 1 diabetic (DB), insulin-controlled Type 1 diabetic (DB-IN), or non-diabetic (Normal) rabbits. Wound healing was monitored, and non-invasive (tonopen, pachymeter, hand-held slit lamp, and retinal camera) and invasive (histopathology) measurements evaluated. Corneal reepithelialization in the uncontrolled DB rabbits was significantly enhanced (up to a 47% reduction in wound area) following treatment with NTX relative to both Normal SV and DB SV rabbits at 24, 48, and 56 h following surgery. At 72 h, DB NTX rabbits had residual defects that were 64-82% smaller than Normal and DB SV animals. NTX treated DB-IN rabbits had residual defects that were 9-37% smaller than DB-IN rabbits receiving SV, and 6-40% smaller than Normal rabbits. No signs of toxicity from topical applications were noted. These data confirm and extend those documented in rats that demonstrated a lack of toxicity of NTX at a wide range of dosages, as well as efficacy for enhanced corneal epithelialization. These studies set the stage for clinical trials using NTX as a therapy for diabetic keratopathy.
角膜延迟再上皮化是糖尿病的一种并发症，可能导致溃疡和糜烂，从而导致眼部发病率和视力丧失。本研究检查了纳曲酮（NTX）的疗效，纳曲酮是一种长效、强效的阿片受体拮抗剂，局部应用可促进糖尿病（链脲佐菌素诱导）新西兰白兔（血糖水平>450mg/dL）标准化角膜擦伤的修复。10(-4)M浓度的 NTX 或无菌载体（SV）每天 4 次局部应用于未控制的 1 型糖尿病（DB）、胰岛素控制的 1 型糖尿病（DB-IN）或非糖尿病（正常）兔子的擦伤眼，持续 7 天。监测伤口愈合情况，并评估非侵入性（眼压计、角膜测厚仪、手持裂隙灯和视网膜相机）和侵入性（组织病理学）测量。与正常 SV 和 DB SV 兔子相比，未经控制的 DB 兔子在手术后 24、48 和 56 小时，使用 NTX 治疗后，角膜再上皮化明显增强（伤口面积减少高达 47%）。在 72 小时时，DB NTX 兔子的残余缺陷比正常和 DB SV 动物小 64-82%。接受 NTX 治疗的 DB-IN 兔子的残余缺陷比接受 SV 的 DB-IN 兔子小 9-37%，比正常兔子小 6-40%。未观察到局部应用的毒性迹象。这些数据证实并扩展了在大鼠中记录的数据，表明 NTX 在广泛的剂量范围内没有毒性，并且对增强角膜上皮化有效。这些研究为使用 NTX 作为糖尿病角膜病变的治疗方法进行临床试验奠定了基础。
