Potential role of Rho-associated protein kinase inhibitor Y-27632 in glaucoma filtration surgery
Potential role of Rho-associated protein kinase inhibitor Y-27632 in glaucoma filtration surgery
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DOI：
10.1167/iovs.07-0878
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发表时间：
2007-12-01
影响因子：
4.4
通讯作者：
Araie, Makoto
中科院分区：
文献类型：
--
作者：
Honjo, Megumi;Tanihara, Hidenobu;Araie, Makoto
目的。目的 研究 Rho 相关蛋白激酶 (ROCK) 特异性抑制剂 Y-27632 在调节人 Tenon 成纤维细胞 (HTF) 活性（包括增殖、粘附、收缩、迁移反应和肌成纤维细胞转分化）中的作用。还在青光眼滤过手术兔模型中检验了 Y-27632 对预防术后疤痕形成的作用。用 Y-27632 处理 HTF 后，研究了细胞毒性、增殖、迁移、粘附和收缩。通过免疫组织化学检查细胞骨架和α-平滑肌肌动蛋白（α-SMA）表达。日本白兔的体内研究包括全层巩膜造口术，然后在术后 7 天期间局部应用 Y-27632。对眼压、滤泡特征的形态变化以及手术部位的组织学进行了评估。结果。 Y-27632对HTF细胞增殖没有直接毒性或显着影响。细胞粘附测定表明，Y-27632 促进了纤连蛋白和 I 型胶原的粘附。使用 Y-27632 显着抑制 HTF 中的胶原凝胶收缩和 α-SMA 表达。 Y-27632 还增加了 HTF 运动性。在体内，与载体相比，Y-27632 抑制滤过手术后的伤口愈合和纤维增殖，并显着改善手术结果。组织学检查显示，Y-27632治疗组中的泡与媒介物治疗组中的泡不同，因为它们在巩膜造口区域中缺乏显着的胶原沉积。结论。 Y-27632 对 HTF 的活性具有深远的影响，并能有效预防青光眼手术兔模型中的纤维增殖和疤痕形成。 ROCK 抑制剂可能是青光眼滤过手术后有效的抗疤痕剂。
PURPOSE. To investigate the role of Y-27632, a specific inhibitor of Rho-associated protein kinase (ROCK) in regulating human Tenon fibroblast (HTF) activities including proliferation, adhesion, contraction, migratory response, and myofibroblast transdifferentiation. Effects of Y-27632 on prevention of postoperative scar formation were also examined in a rabbit model of glaucoma filtration surgery.METHODS. After treatment of HTFs with Y-27632, cell toxicity, proliferation, migration, adhesion, and contraction were studied. The cytoskeleton and alpha-smooth muscle actin (alpha-SMA) expression were examined via immunohistochemistry. In vivo studies in Japanese white rabbits consisted of a full-thickness sclerostomy followed in the 7-day postoperative period by topical application of Y-27632. Intraocular pressure, morphologic changes in bleb features, and histology of surgical sites were evaluated.RESULTS. Y-27632 had no direct toxicity or significant effects on cell proliferation of HTF. The cell adhesion assay showed that Y-27632 promoted adhesiveness to both fibronectin and collagen type I. Use of Y-27632 significantly inhibited collagen gel contraction and alpha-SMA expression in HTFs. Y-27632 also increased HTF motility. In vivo, Y-27632 inhibited wound healing and fibroproliferation after filtration surgery and significantly improved surgical outcome compared with the vehicle. Histologic examination revealed that blebs in the Y-27632treated group differed from those in the vehicle-treated group in that they lacked significant collagen deposition in the sclerostomy area.CONCLUSIONS. Y-27632 had profound effects on activities of HTFs and was effective in preventing fibroproliferation and scar formation in a rabbit model of glaucoma surgery. A ROCK inhibitor may be an effective anti-scarring agent after glaucoma filtering surgery.