Oydanich Marko, Epstein Seth P, Gadaria-Rathod Neha, Guers John J, Fernandez Karen B, Asbell Penny A
a Department of Ophthalmology , Mount Sinai Medical Center , New York , New York , USA.
b Department of Exercise Science , Stockton University , Galloway , New Jersey , USA.
Curr Eye Res. 2018 Oct;43(10):1215-1220. doi: 10.1080/02713683.2018.1490772. Epub 2018 Jul 17.
Purpose/Aim: Corneal abrasions and nonhealing corneal epithelial defects are common conditions that cause pain and sometimes are slow to heal. Histatins, a family of histidine-rich peptides, have been implicated in oral and skin epithelial wound healing, and have been shown to be effective in vitro in human corneal epithelial cells. The objective of this study was to test the efficacy of histatin-1 on corneal epithelial wound healing in rabbits.
MATERIALS & METHODS: Twenty-two (22) rabbits were separated into four treatment groups, each containing 3-7 rabbits. Treatments included three histatin-1 formulations (0.1 ug/ml. 1 ug/ml, and 10 ug/ml) and one inactive vehicle, one drop given three times per day. Eight (8) mm circular wounds were created using 0.5 ml of 20% ethyl alcohol in the right eye of each rabbit. A masked observer photographed each eye twice daily using slit-lamp biomicrophotography. Wound area was analyzed by using ImageJ. Statistical analysis was conducted using Graphpad Prism.
Wound recovery was faster in animals given 0.1 ug/ml, 1 ug/ml, and 10 ug/ml when compared to the vehicle solution at 6, 24, and 30 hours after wound creation (p < 0.01). No adverse events were observed in any eyes. When analyzing area under the curve, % recovered area was higher overall in the 0.1 ug/ml (p < 0.01), 1 ug/ml (p < 0.01), and 10 ug/ml (p < 0.001) groups when compared to the vehicle solution. Hourly healing rate was also observed to be faster in the 0.1 ug/ml, 1 ug/ml, and 10 ug/ml groups (p < 0.001) at 24 hours postinjury suggesting an accelerated healing process as compared to the vehicle group.
This study represents the first in vivo experiment evaluating and confirming the efficacy of topical histatin on the corneal epithelium wound healing. Further studiesare warranted to better understand the mechanism and safety of topical histatin-1 in corneal epithelial wound-healing and its potential role for human disease treatment.
目的/目标:角膜擦伤和不愈合的角膜上皮缺损是常见病症,会引起疼痛,有时愈合缓慢。富组蛋白是一类富含组氨酸的肽,已被证明与口腔和皮肤上皮伤口愈合有关,并且在体外对人角膜上皮细胞有效。本研究的目的是测试组蛋白-1对兔角膜上皮伤口愈合的疗效。
22只兔子被分成四个治疗组,每组包含3-7只兔子。治疗包括三种组蛋白-1制剂(0.1微克/毫升、1微克/毫升和10微克/毫升)和一种无活性载体,每天滴眼三次,每次一滴。使用0.5毫升20%乙醇在每只兔子的右眼制造8毫米圆形伤口。一名蒙面观察者每天使用裂隙灯生物显微镜摄影对每只眼睛拍摄两次。使用ImageJ分析伤口面积。使用Graphpad Prism进行统计分析。
与赋形剂溶液相比,给予0.1微克/毫升、1微克/毫升和10微克/毫升组的动物在伤口形成后6、24和30小时伤口愈合更快(p<0.01)。在任何眼睛中均未观察到不良事件。在分析曲线下面积时,与赋形剂溶液相比,0.1微克/毫升(p<0.01)、1微克/毫升(p<0.01)和10微克/毫升(p<0.001)组的总体愈合面积百分比更高。在损伤后24小时,0.1微克/毫升、1微克/毫升和10微克/毫升组的每小时愈合率也更快(p<0.001),表明与赋形剂组相比愈合过程加快。
本研究是第一项评估和确认局部应用组蛋白对角膜上皮伤口愈合疗效的体内实验。有必要进行进一步研究以更好地了解局部应用组蛋白-1在角膜上皮伤口愈合中的机制和安全性及其在人类疾病治疗中的潜在作用。