Transforming Growth Factor Alpha (TGF-a) Induced Angiogenesis: Direct Versus Indirect

The objective of this study was to determine the angiogenic potential of transforming growth factor-alpha (TGF-a). Recombinant human TGF-a (0.25 to 5.0 ug) was implanted in the rabbit cornea. The eyes were monitored daily for corneal opacification, dilation of limbal blood vessels, and the growth of new capillaries toward the implanted TGF-a. Two, 3 and 7 days post-implantation, the eyes were harvested for histology, transmission electron microscopy, or examination of vascular corrosion casts with scanning electron microscopy. TGF-a (2.5-5.0 ug) consistently elicited an influx of inflammatory cells followed by capillary formation. To determine if these inflammatory cells were the initiators and mediators of the angiogenic response, they were depleted by local administration of methylprednisolone acetate (MPA). The angiogenesis was reduced, but not completely blocked. These results suggest that TGF-a is capable of directly stimulating neovascularization. However, the direct angiogenesis appears to be augmented by the products of the recruited inflammatory cells.