Department of Ophthalmology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
Kaohsiung J Med Sci. 2013 Jul;29(7):353-61. doi: 10.1016/j.kjms.2012.11.002. Epub 2013 Jan 12.
Inhibiting the healing of wounds to ensure that the aqueous humor can drain into the scleral space unimpeded and form a filtering bleb plays a crucial role in determining the success rate of glaucoma surgery. The aim of this study was to investigate the novel use, with cell culture and animal models, of some commercial intraocular pressure (IOP)-lowering drugs in inhibiting the healing of fibroblast wounds. The Tenon's fibroblasts of rabbits were cultured to evaluate 13 IOP-lowering drugs for cellular proliferation, collagen formation, and migration. These were measured using [(3)H]thymidine and [(3)H]proline uptake, and Transwell chambers. A preservative of benzalkonium chloride (BAK) was initially used, with 0.02% as a maximal original concentration. All of the drugs and the BAK were diluted from original commercial concentrations to 1/10, 1/100, and 1/1000. The more inhibitive drugs screened from the cell cultures were then selected for further short-term application during and after trabeculectomy surgeries had been performed on the rabbits. Expression of the proliferative cell nuclear antigen was immunohistochemically examined 3 and 7 days after surgery. The results revealed that the inhibitive effects of BAK in cellular [(3)H]thymidine and [(3)H]proline uptake, and cellular migration were only evident at 0.002% concentrations. Based on the results of the cell cultures, timolol, latanoprost, and unoprostone exhibited a greater inhibitory effect than the other drugs. Moreover, the animal studies showed that latanoprost and unoprostone significantly suppressed the positive expression of proliferative cell nuclear antigen around the operative excision area 7 days after the trabeculectomy surgeries. The results indicate that short-term use of some IOP-lowering drugs, such as latanoprost and unoprostone, may inhibit postoperative wound healing after glaucoma surgery.
抑制伤口愈合，确保房水无障碍地流入巩膜间隙并形成过滤泡，这对于确定青光眼手术的成功率至关重要。本研究旨在通过细胞培养和动物模型，探索一些市售降眼压药物在抑制成纤维细胞伤口愈合方面的新用途。我们培养兔的 Tenon 氏成纤维细胞，评估 13 种降眼压药物对细胞增殖、胶原形成和迁移的作用。通过 [(3)H]胸腺嘧啶核苷和 [(3)H]脯氨酸摄取以及 Transwell 室来测量这些作用。最初使用苯扎氯铵（BAK）作为防腐剂，最大原始浓度为 0.02%。所有药物和 BAK 均从原始商业浓度稀释至 1/10、1/100 和 1/1000。从细胞培养中筛选出更具抑制作用的药物，然后在对兔进行小梁切除术期间和之后的短期应用中进行选择。手术后 3 天和 7 天，通过免疫组织化学检查增殖细胞核抗原的表达。结果表明，BAK 在细胞 [(3)H]胸腺嘧啶核苷和 [(3)H]脯氨酸摄取以及细胞迁移中的抑制作用仅在 0.002%浓度时才明显。基于细胞培养的结果，噻吗洛尔、拉坦前列素和乌诺前列素的抑制作用大于其他药物。此外，动物研究表明，拉坦前列素和乌诺前列素在小梁切除术后 7 天明显抑制了手术切除区域周围增殖细胞核抗原的阳性表达。这些结果表明，短期使用一些降眼压药物，如拉坦前列素和乌诺前列素，可能会抑制青光眼手术后的术后伤口愈合。
