Corneal safety of topically applied naltrexone.
Corneal safety of topically applied naltrexone.
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局部应用纳曲酮的角膜安全性。
DOI：
10.1089/jop.2006.22.377
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
McLaughlin,PatriciaJ
中科院分区：
文献类型：
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作者：
Zagon,IanS;Klocek,MatthewS;Sassani,JosephW;Mauger,DavidT;McLaughlin,PatriciaJ
目的：纳曲酮（NTX）是一种阿片类拮抗剂，能促进正常和糖尿病动物角膜上皮的创面愈合。本研究通过角膜局部应用来检验NTX的安全性。方法：将浓度为10-3、10-4、10-5、10-6或10-7M的NTX局部给予1型糖尿病大鼠（血糖水平bb0 ~ 400mg /dL） （DB）、接受胰岛素维持正常血糖（DB- in）的DB动物和糖尿病发病后8周开始的正常（非糖尿病）（normal）受试者，每天4次，持续7 d。结果：在接受和未接受NTX治疗的DB组、DB- in组和Normal组之间，眼压、角膜厚度、内皮细胞数量、上皮细胞凋亡、坏死或组织均无差异。在NTX治疗前，DB组的角膜敏感性比正常组和DB- in组降低了两倍，但在慢性暴露于10 - 3至10-7M的NTX终止后至少2周与正常组和DB- in组相当。正常组和DB-IN组之间没有差异。结论：局部应用超过10,000倍剂量范围的NTX对所研究的参数没有明显的毒性，表明使用NTX进行角膜伤口愈合的疗效研究是有必要的。
Purpose: Naltrexone (NTX), an opioid antagonist, accelerates wound healing of corneal epithelium in normal and diabetic animals. This study examined the safety of NTX by topical application in the cornea.Methods: NTX in concentrations of 10–3, 10–4, 10–5, 10–6, or 10–7M was administered topically 4 times/daily for 7 d to the eye of Type 1 diabetic rats (glucose levels >400 mg/dL) (DB), DB animals receiving insulin to maintain normoglycemia (DB-IN), and normal (nondiabetic) (Normal) subjects beginning 8 weeks after onset of diabetes.Results: No differences in intraocular pressures, corneal thickness, endothelial cell number, or epithelial apoptosis, necrosis, or organization were observed between DB, DB-IN, and Normal groups with and without treatment with NTX. The DB group had a twofold decrease in corneal sensitivity from the Normal and DB-IN groups prior to NTX treatment but were comparable to the Normal and DB-IN groups for at least 2 weeks after chronic exposure to 10–3to 10–7M NTX was terminated. No differences between Normal and DB-IN groups were noted.Conclusions: Topical application of NTX over a 10,000-fold range of dosage had no overt toxicity for the parameters studied, indicating that efficacy studies for the use of NTX in corneal wound healing are warranted.