Lipid hydroperoxide stimulates retinal neovascularization in rabbit retina through expression of tumor necrosis factor-α, vascular endothelial growth factor and platelet-derived growth factor

被引:50
作者
Armstrong D. [1 ,7 ]
Ueda T. [1 ]
Ueda T. [1 ]
Aljada A. [1 ]
Browne R. [1 ]
Fukuda S. [1 ]
Spengler R. [2 ]
Chou R. [2 ]
Hartnett M. [3 ]
Buch P. [3 ]
Dandona P. [4 ]
Sasisekharan R. [5 ]
Dorey C.K. [6 ]
机构
[1] Dept. of Clinical Laboratory Science, State University of New York, Buffalo
[2] Department of Pathology, State University of New York, Buffalo
[3] Department of Ophthalmology, State University of New York, Buffalo
[4] Department of Medicine, State University of New York, Buffalo
[5] Div. of Hlth. Sci. and Technology, Harvard University, Massachusetts Inst. of Technology, Cambridge
[6] Schepens Eye Research Institute, Harvard Medical School, Boston
[7] Dept. of Clinical Laboratory Science, State Univ. of New York at Buffalo, 26 Cary Hall, 3435 Main Street, Buffalo
关键词
Lipid hydroperoxidase; Neovascularization; Platelet-derived growth factor; Tumor necrosis factor-α; Vascular endothelial growth factor;
D O I
10.1023/A:1009010628371
中图分类号
学科分类号
摘要
To test the hypothesis that oxidative damage associated with tissue hypoxia plays a role in neovascularization, a lipid hydroperoxide (LHP) was injected into the vitreous of rabbits. Single injections of LHP (50-600 μg) caused a sustained retinal neovascularization visualized clinically by ophthalmoscopy and confirmed by microscopy. Vasodilators, i.e. histamine and nitric oxide, peaked at 6 h and 7 days, respectively. The levels of both tumor necrosis factor-α and interleukin-Iα peaked at 12 h and dropped to basal levels by 24 h. Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β peaked at 24 h and were sustained throughout the following 3 weeks, and platelet-derived growth factor was also elevated throughout the same period. Up-regulation of these five angiogenic cytokines, but not basic fibroblast growth factor, occurred prior to the appearance of neovascularization. Leakage of fluorescein at the tips of new vessels was demonstrated by fluorescein angiography. Linoleic hydroperoxide induced neovascularization, but saturated or unsaturated native C-18 fatty acids had no effect. The cascade of multiple, angiogenic cytokines induced by LHP may interact to promote sustained neovascularization. [© 1998 Rapid Science Ltd.].
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页码:93 / 104
页数:11
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