Abstract
Purpose: :
To examine the role of tumor necrosis factor alpha (TNFalpha) in regulation of neovascularization in vitro and in vivo.
Methods: :
(1) The co–culture system of human fibroblasts and human umbilical vein endothelial cells was used to examine the roles of cytokines in new vessel formation. The co–cultures were incubated in the presence or absence of each of TNFalpha or TGFbeta1. Development of endothelial cell tube was observed. (2) The central part of one cornea of adult C57BL/6 (WT) mice or TNFalpha–null mice was cauterized to induce neovascularization from limbus. At 7, 14, and 21 days the animals were killed and the eye was enucleated. Stromal neovascularization was examined by histology and immunohistochemistry.
Results: :
(1) Adding TNFalpha inhibited formation of new vessel–like endothelial cell tube in the presence and absence of TGFbeta1.(2) Development of neovascularization from the limbus was more marked in TNFalpha–null mice as compared with WT mice at day 7 as revealed by PECAM–immunostaining. Expression of VEGF and TGFbeta1 was also more marked in KO mouse corneas than in WT corneas.
Conclusions: :
TNFalpha counteracts the behavior of endothelial cells to form a cell tube in vitro and also suppresses corneal neovascularization in vivo.
Keywords: cornea: basic science • neovascularization • growth factors/growth factor receptors