The Effect of Everolimus on Scar Formation in Glaucoma Filtering Surgery in a Rabbit Model

Purpose: To investigate the efficiency of everolimus on the prevention of postoperative scar in a rabbit model of glaucoma filtering surgery in comparison with mitomycin-C (MMC).Materials and Methods: Thirty New Zealand albino rabbits were randomly assigned into 3 groups, each including ten rabbits: an everolimus group (Group 1), a MMC group (Group 2), and a sham group (Group 3). A limbal-based trabeculectomy was performed on the right eyes of all the rabbits. For 28 days following surgery, the eyes were evaluated in terms of intraocular pressure (IOP), morphological and biomicroscopic changes, and complications in the bleb. On the 28th day, four eyes randomized from each group were enucleated and histologically and immunohistochemically analyzed. Transforming growth factor-β1 (TGF-β1), metalloproteinase (MMP-2, MMP-9), and proliferative cell nuclear antigen (PCNA) expressions in each group were evaluated. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis.Results: Bleb survival was statistically significantly longer for a period in Group 1 compared to Group 2. When postoperative IOPs of three groups were measured, it was seen that there is significant IOP reduction in all three groups. However, there were increases in the mean IOP values beginning from the 5th day in Group 2 and from the 3rd day in Group 3 while in Group 1 mean IOP values began to increase beginning from 10th day and the mean IOP values in Group 1 remained at a lower level in comparison to the other groups for 28 days (p p Conclusion: Everolimus appears to suppress the proliferation of fibroblast and thus may provide an effective treatment strategy in glaucoma filtering surgery.研究目的：本研究旨在以青光眼滤过手术兔模型为研究对象，对比依维莫司（everolimus）与丝裂霉素-C（MMC）预防术后瘢痕的疗效。 材料与方法：将30只新西兰白化兔随机分为3组，每组10只：依维莫司组（第1组）、MMC组（第2组）及假手术组（第3组）。对所有家兔右眼实施角膜缘小梁切除术。术后28天内，通过眼压（intraocular pressure, IOP）检测、形态学观察、裂隙灯生物显微镜检查及滤过泡并发症评估对术眼进行监测。术后第28天，从每组随机选取4只家兔摘除眼球，进行组织学及免疫组织化学分析。检测各组转化生长因子-β1（transforming growth factor-β1, TGF-β1）、金属蛋白酶（metalloproteinase, MMP-2、MMP-9）及增殖细胞核抗原（proliferative cell nuclear antigen, PCNA）的表达水平；采用脱氧核糖核苷酸末端转移酶介导的dUTP缺口末端标记法（terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, TUNEL）检测细胞凋亡情况。 结果：第1组的滤过泡存活时长较第2组显著更长。对三组术后眼压进行检测可见，三组均出现显著的眼压降低。但第2组自术后第5日、第3组自术后第3日起平均眼压出现升高；而第1组平均眼压自术后第10日起才开始升高，且术后28天内其平均眼压水平均低于其余两组（P<0.05）。 结论：依维莫司可抑制成纤维细胞增殖，有望成为青光眼滤过手术中有效的防治策略。