The trial of treatment in choroidal neovascularization by the drug release system of NK4,inhibitors of hepatocyte growth factor

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14571682
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Nagoya City University
• Principal Investigator: OKUDA Masatoshi Nagoya City University, Graduate School of Medical Sciences, Research Assistant, 大学院・医学研究科, 助手 (70336684)
• Co-Investigator(Kenkyū-buntansha): MORITA Hiroshi Nagoya City University, Graduate School of Medical Sciences, Research Assistant, 大学院・医学研究科, 助手 (20363947) ; YOSHIDA Munenori Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (60273447) ; OGURA Yuichiro Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院・医学研究科, 教授 (70191963)
• Project Period (FY): 2002 – 2003
• Keywords: NK4 / HGF / Biodegradable scleral implant / Drug delivery system / HUVEC / CNV

Research Abstract

Hepatocyte growth factor (HGE) is shown growth promoting action as much as VEGF (vascular endothelial growth factor) or bFGF (basic fibroblast growth factor) to the human umbilical vein endothelial cells (HUVEC). It is becoming clear that NK4,which is the antagonist of the HGF, inhibits the neovascularization was induced VEGF and bFGF.
(1)We evaluated the proliferating suppression effect of NK4 to the HUVEC and the human retinal pigment epithelial cell (ARPE-19). On the 96 well plates, each hole was scattered 1x10^3 each cells. It was made to expose for 72 hours to the NK4 of the concentration of 5,10,50,100,500 nM. We evaluated the cellular proliferating suppression effect by using a XTT assay. NK4,50 nM or more, contrastively controlled to HUVEC. On the other hand, Any concentration of NK4 was not influenced ARPE-19. Therefore, it was suggested that a cellular proliferation suppression effect of NK4 was specific action to vascular endothelial cells and controlled only neovascularization without affecting its surrounding cells.
(2)We evaluated the suppression effect of NK4 to the experimental choroidal neovascularization. Experimental CNV was induced in rats by laser photocoagulation, and 5μl (10μM) of NK4,dissolved in BSS, was injected in the vitreous cavity. Controls received a intravitreal injection 5ml of only BSS. We performed fluorescein angiography 2nd weeks after photocoagulation, and we evaluated the formation of CNV. It measured the thickness of the CNV with light microscope. As compared with contrast, the difference was not seen conclusively.