Kwon Young Sam, Kim Jae Chan
Department of Ophthalmology, Chung-Ang University, Yongsan Hospital, College of Medicine, Seoul 140-757, Korea.
Exp Mol Med. 2006 Apr 30;38(2):173-9. doi: 10.1038/emm.2006.21.
The purpose of this study was to determine whether rapamycin could inhibit corneal angiogenesis induced by basic fibroblast growth factor (bFGF). Using human dermal microvascular endothelial cells (HDMECs), we examined the effect of rapamycin on cell proliferation and migration, and the expression of vascular endothelial growth factor (VEGF). The rabbit's eye was implanted intrastromally into the superior cornea with pellet containing bFGF for the control group and pellet containing bFGF and rapamycin for the rapamycin group. Biomicrographically, corneal angiogenesis was evaluated for 10 days after pellet implantation. The neovascularized cornea also was examined histologically. bFGF induced corneal neovascularization was significantly reduced by treatment with rapamycin. Using in vitro model, rapamycin strongly inhibited bFGF induced proliferation, migration, and VEGF secretion of HDMECs. We could observe that the bFGF induced corneal angiogenesis was inhibited by rapamycin in a micropocket rabbit model. The score of neovascularization was significantly decreased in the rapamycin group than in the control group at 10 days after pellet implantation. Histologically, the cornea of rapamycin group also showed much less new vessels than that of control group. Collectively, rapamycin appears to inhibit bFGF induced angiogenesis in a rabbit corneal micropocket assay and may have therapeutic potential as an antiangiogenic agent.
本研究的目的是确定雷帕霉素是否能够抑制碱性成纤维细胞生长因子（bFGF）诱导的角膜血管生成。我们使用人真皮微血管内皮细胞（HDMECs），检测了雷帕霉素对细胞增殖、迁移以及血管内皮生长因子（VEGF）表达的影响。对照组将含bFGF的药粒基质内植入兔眼上角膜，雷帕霉素组则植入含bFGF和雷帕霉素的药粒。通过活体显微镜观察，在植入药粒后10天对角膜血管生成进行评估。对新生血管化的角膜也进行了组织学检查。雷帕霉素治疗可显著减少bFGF诱导的角膜新生血管形成。利用体外模型，雷帕霉素强烈抑制bFGF诱导的HDMECs增殖、迁移及VEGF分泌。我们观察到在微袋兔模型中雷帕霉素可抑制bFGF诱导的角膜血管生成。在植入药粒10天后，雷帕霉素组的新生血管化评分显著低于对照组。组织学检查显示，雷帕霉素组角膜的新生血管也比对照组少得多。总体而言，在兔角膜微袋试验中雷帕霉素似乎可抑制bFGF诱导的血管生成，并且作为一种抗血管生成剂可能具有治疗潜力。
