Exp Mol Med.  2006 Apr;38(2):173-179.

Inhibition of corneal neovascularization by rapamycin

• Kwon YS
• Kim JC

Abstract

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.

Keyword

cornea; neovascularization; rabbit; rapamycin; vascular endothelial growth factor

MeSH Terms

Vascular Endothelial Growth Factor A/biosynthesis
Sirolimus/pharmacokinetics/*pharmacology
Rabbits
Humans
Fibroblast Growth Factor 2/pharmacokinetics/pharmacology
Female
Endothelial Cells/cytology/drug effects/metabolism
Drug Implants
Dose-Response Relationship, Drug
Corneal Neovascularization/*drug therapy/pathology
Cells, Cultured
Cell Proliferation/drug effects
Cell Movement/drug effects
Animals
Angiogenesis Inhibitors/pharmacokinetics/*pharmacology