Impaired Angiogenic Response in the Corneas of Mice Lacking Osteopontin

• Published in: Investigative ophthalmology & visual science 2010-02, Vol.51 (2), p.790-794
• Main Authors: Fujita, Norihito, Fujita, Shuko, Okada, Yuka, Fujita, Kyoko, Kitano, Ai, Yamanaka, Osamu, Miyamoto, Takeshi, Kon, Shigeyuki, Uede, Toshimitsu, Rittling, Susan R, Denhardt, David T, Saika, Shizuya
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Cells, Cultured; Cornea - cytology; Corneal Neovascularization - etiology; Corneal Neovascularization - metabolism; Corneal Neovascularization - prevention & control; Corneal Stroma - blood supply; Fibroblasts - cytology; Fibroblasts - metabolism; Macrophages, Peritoneal - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteopontin - pharmacology; Osteopontin - physiology; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Signal Transduction; Transforming Growth Factor beta1 - metabolism; Up-Regulation; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.09-3420

To investigate the effects of loss of osteopontin (OPN) in the development of neovascularization in corneal stroma in mice. Cell culture study was also conducted to clarify the effects of OPN in transforming growth factor (TGF) beta1-driven cell signaling and expression of vascular endothelial growth factor (VEGF). Ocular fibroblasts from wild-type and OPN-null mice were used to study the role of OPN in TGFbeta1 signal and VEGF expression. The effect of the absence of OPN on corneal neovascularization was evaluated in mice. In ocular fibroblast culture, loss of OPN attenuated TGFbeta1 signals (Smad3 and p38) and reduced expression of VEGF. Loss of OPN attenuated neovascularization in corneal stroma in mice. OPN is involved in VEGF expression in cultured fibroblasts and is required for neovascularization in corneal stroma in vivo.