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Shuko Fujita, Shizuya Saika, Winston Whei-Yang Kao, Kyoko Fujita, Takeshi Miyamoto, Kazuo Ikeda, Yuji Nakajima, Yoshitaka Ohnishi; Endogenous TNFα Suppression of Neovascularization in Corneal Stroma in Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(7):3051-3055. doi: https://doi.org/10.1167/iovs.06-1083.
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purpose. To examine the role of tumor necrosis factor α (TNFα) in stromal neovascularization in injured cornea in vivo and in cytokine-enhanced vessel-like endothelial cell tube formation in vitro.
methods. An in vitro model of angiogenesis was used to examine the roles of TNFα on tube formation by human umbilical vein endothelial cells (HUVECs) cocultured with fibroblasts on induction by transforming growth factor β1 (TGFβ1) and vascular endothelial growth factor (VEGF). Central cauterization was used to induce stromal neovascularization in corneas of wild-type (WT) and TNFα-null (Tnfα–/–) mice. At 7, 14, or 21 days of injury, experimental mice were killed, and the eyes were enucleated and subjected to histologic and immunohistochemical examination and real-time reverse transcription–polymerase chain reaction.
results. HUVECs formed a vessel-like tube structure on the fibroblast feeder layer. Adding TGFβ1, VEGF, or both augmented vessel-like tube formation by HUVECs cocultured with fibroblasts. Adding TNFα (5 ng/mL) completely abolished the formation of tube-like structures despite the presence or absence of TGFβ1 or VEGF in coculture. In vivo, cauterization of the central cornea induced the formation of CD31+ new vessels surrounding the limbus in WT mice. More prominent central stromal neovascularization accompanied by increased expression of TGFβ1 and VEGF was found in Tnfα–/– mice compared with WT mice.
conclusions. In addition to inhibiting TGFβ1 and VEGF expression by fibroblasts, endogenous TNFα may counter the induction effects of TGFβ1 and VEGF on vascular endothelial cells and may block neovascularization.
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