准分子激光屈光性角膜切削术后兔角膜基质细胞凋亡及其防治的研究

目的：探讨准分子激光屈光性角膜切削术（photorefractive keratectomy,PRK）后凋亡机制介导的角膜创伤愈合反应对屈光度数回退和角膜雾状混浊（haze）的影响,以及局部应用锌制剂的药物效果。方法：对90只新西兰白兔行双眼PRK,将左眼作为实验眼,手术前、后分别给予A组0．1％地塞米松眼液、B组0．5％硫酸锌眼液和C组0．04％丝裂霉素眼液滴眼;右眼作为对照眼。术后定期裂隙灯下观察haze的程度,测量角膜的厚度,进行光镜和透射电镜观察,采用脱氧三磷酸尿苷缺口末端标记法行凋亡细胞检测,并进行对比性分析。结果：（1）PRK术后角膜前基质细胞出现凋亡,实验眼B组凋亡细胞最少（P＜0．01）。（2）术后角膜厚度增加,前基质细胞增多,实验眼haze和增生程度眼B组凋亡细胞最少（P＜0．01）。（3）术后角膜上皮增生,实验眼B组角膜上皮厚度最小（P＜0．01）。结论：PRK术后屈光度数回退和haze的形成是凋亡机制介导的角膜创伤愈合过程,锌制剂可阻止角膜前基质细胞凋亡,最大限度减轻反应性过度增生,有望成为临床防治haze形成和屈光度数回退的理想药物。

Mechanism and treatments of regression and haze after photorefractive keratectomy

Objectives To investigate the effects of apoptosis induced corneal wound healing response on regression and haze after photorefractive keratectomy as well as the influence of zinc on the cornea having undergone PRK. Methods Ninety rabbits divided into three groups underwent bilateral 193 nm excimer laser photorefractive keratectomy. The eyes were treated perioperatively with 0 1% flumetholon, 0 04% mitomycin C (MMC) or 0 5% zinc sulfate, and 0 9% NaCl solution as control. Comparative studies on haze, corneal thickness, histopathology and apoptosis were made periodically after operation. Results (1) Apoptosis was detected remarkably in anterior keratocytes at 4 hours, 2 weeks, 1 month after PRK. The level of keratocyte apoptosis in ZnSO 4 group was the least among all the groups ( P <0 01). (2) Corneal thickness and the number of keratocytes were increased after operation. The level of proliferation and haze was the highest in the control group and lowest in both MMC group and ZnSO 4 group ( P <0 01). (3) Corneal epithelial cells were proliferated after operation. The epithelial thickness was the least in ZnSO 4 group ( P <0 01). There were no statistical differences among others ( P >0 05). Conclusions Regression and haze after PRK may result from the corneal wound healing response, which probably is initiated by keratocyte apoptosis. Zinc can inhibit apoptosis, glucocorticoids and MMC can prevent the over proliferation, all of them can reduce regression and haze after PRK, while topical zinc application may become a kind of safe and effective way in the future.