Inhibition by methylprednisolone acetate suggests an indirect mechanism for TGF-B induced angiogenesis.
Angiogenesis induced by transforming growth factor beta (TGFB) implanted in the rabbit cornea is accompanied by an influx of inflammatory cells. To determine if the inflammatory cells are the mediators of the neovascularization, they were depleted by local administration of methylprednisolone acetate (MPA). Subconjunctival injections of 16 mg of MPA immediately following implantation of 50 ng of TGFB in the cornea prevented the inflammation and subsequent formation of capillaries. If the injections of MPA were delayed by 48 hr and the inflammatory cells were allowed to enter the cornea, angiogenesis occurred, demonstrating that MPA had no adverse effects on the ability of endothelial cells to form capillaries. These results confirm the hypothesis that TGFB induces angiogenesis indirectly by recruiting inflammatory cells capable of stimulating direct angiogenesis.
Phillips
G D
GD
Department of Surgery, University of Minnesota, Minneapolis 55455.
Whitehead
R A
RA
Knighton
D R
DR
D000818:Animals; D003315:Cornea / Q000187:drug effects; D004343:Drug Implants; D006801:Humans; D020100:Hydrogels; D007249:Inflammation; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077555:Methylprednisolone Acetate; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000473:pathology; D011102:Polyhydroxyethyl Methacrylate / Q000031:analogs & derivatives; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D004343:Drug Implants; D020100:Hydrogels; D016212:Transforming Growth Factor beta; C000257:polyhydroxyethyl methacrylate hydrogels; D011102:Polyhydroxyethyl Methacrylate; D000077555:Methylprednisolone Acetate; D008775:Methylprednisolone