Mitomycin C-induced reduction of keratocytes and fibroblasts after photorefractive keratectomy
Mitomycin C-induced reduction of keratocytes and fibroblasts after photorefractive keratectomy
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DOI：
10.1167/iovs.04-0070
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Tchah, H
中科院分区：
文献类型：
--
作者：
Kim, TI;Pak, JH;Tchah, H
目的。探讨丝裂霉素C（MMC）对屈光性角膜切除术（PRK）和中波紫外线（UV-B）照射后角膜细胞数量和成纤维细胞增殖的影响。第 1、2、3 组新西兰白兔（每组 18 只）的右眼接受 PRK，以 5 mm 光学区矫正 -10 屈光度。将浸有0.02％MMC的海绵应用于第1组兔子的右眼2分钟。所有兔子每天使用抗生素软膏直至上皮完全愈合，然后第2组的右眼每天使用0.02% MMC滴眼液两次，直至PRK后4周。 PRK后三周，所有剩余兔子的右眼暴露于100 mJ/cm(2) C UV-B辐射。每 3 周使用 Fantes 量表通过生物显微镜评估角膜混浊度。 PRK后3、6、12周各组6只眼摘除，组织标本用苏木精、伊红和TUNEL染色。使用抗α-平滑肌肌动蛋白（SMA）的抗体对组织进行免疫组织化学评估。通过电子显微镜评估前基质和上皮基底膜的细胞变化。结果。 PRK后观察到角膜混浊，并因UV-B照射而加剧。 PRK 后立即术中应用 MMC 诱导角膜细胞混浊和凋亡。 PRK 后 12 周，即使在 UV-B 照射后，MMC 也能显着减少角膜混浊、角膜细胞、凋亡细胞和成纤维细胞的数量。即使在 12 周后，仅在 PRK 处理的、非 MMC 处理的兔子（第 3 组）中发现相对大量的凋亡和 SMA 阳性细胞。 PRK后三周，垂死的基质细胞出现细胞收缩，并且通过电子显微镜在所有处理组中观察到染色质浓缩。 PRK 后 12 周，与其他组相比，第 1 组上皮层下方观察到的角膜细胞和炎症细胞较少。结论。 MMC 是 PRK 引起的角膜混浊的有效抑制剂。 PRK 和 UV-B 照射后，MMC 减少了角膜细胞和成纤维细胞的数量。虽然MMC会改善PRK的临床效果，但它对角膜角膜细胞有明显的毒性，直到PRK后3个月才消失。
PURPOSE. To investigate the effects of mitomycin C (MMC) on the number of keratocytes and the proliferation of fibroblasts after photorefractive keratectomy (PRK) and exposure to ultraviolet B (UV-B) irradiation.METHODS. The right eyes of New Zealand White rabbits in Groups 1, 2, and 3 (n = 18 each) underwent PRK to correct -10 diopters with 5 mm optical zone. Sponges soaked with 0.02% MMC were applied to the right eyes of Group 1 rabbits for 2 minutes. Antibiotic ointment was applied daily to all rabbits until the epithelium healed completely, after which 0.02% MMC eye drops were applied twice daily to the right eyes in Group 2 until 4 weeks after PRK. Three weeks after PRK, the right eyes of all the remaining rabbits were exposed to 100 mJ/cm(2) C UV-B radiation. Corneal haziness was assessed biomicroscopically using the Fantes scale every 3 weeks. Six eyes of each group were each enucleated 3, 6, and 12 weeks after PRK, and tissue specimens were stained with hematoxylin and eosin and with TUNEL stain. The tissues were evaluated immunohistochemically with antibody to alpha-smooth muscle actin (SMA). Cellular changes in the anterior stroma and epithelial basement membrane were evaluated by electron microscopy.RESULTS. Corneal haze was observed after PRK and was aggravated by UV-B irradiation. A single intraoperative application of MMC immediately after PRK induced opacity and apoptosis of keratocytes. Twelve weeks after PRK, MMC significantly reduced corneal haze, the number of keratocytes, apoptotic cells, and fibroblasts, even after UV-B irradiation. Relatively large numbers of apoptotic and SMA-positive cells were found only in PRK-treated, non-MMC treated rabbits (Group 3), even after 12 weeks. Three weeks after PRK, dying stromal cells showed cell shrinkage, and chromatin condensation was observed in all treated groups by electron microscopy. Twelve weeks after PRK, fewer keratocytes and inflammatory cells were observed just beneath the epithelial layer in Group 1 than in any of the other groups.CONCLUSIONS. MMC is a potent inhibitor of corneal haze induced by PRK. MMC reduced the number of keratocytes and fibroblasts after PRK and UV-B irradiation. Although MMC would improve the clinical results of PRK, it has significant toxicity on corneal keratocytes, which did not disappear until 3 months after PRK.