Growth factors in new blood vessel growth and AMD Therapy

Xuri Li, PhD
The National Eye Institute (Bethesda, MD)
Year Awarded:
2007
Grant Duration:
April 1, 2007 to May 31, 2009
Disease:
Macular Degeneration
Award Amount:
$100,000
Grant Reference ID:
M2007051
Award Type:
Standard
Award Region:
US Northeastern
Xuri Li, PhD

PDGF-C/D in Choroidal Neovascularization and AMD Therapy

Summary

This project will test the role of two growth factors, PDGF-C and PDGF-D, in the development and growth of new blood vessels in the choroids and retina. Inhibition of these molecules may provide possible new therapies for AMD.

Details


Reagents that can suppress the growth of undesired blood vessels have shown beneficial effects for some AMD patients. However, none of them can halt or reverse the course of the disease. New anti-angiogenic reagents are therefore still needed. The platelet-derived growth factor C (PDGF-C) and PDGF-D are two promising candidate molecules to be targeted. Our previous and current work has shown that both PDGF-C and PDGF-D are potent angiogenic factors with potential important roles in choroidal neovascularization (CNV). This study is thus designed to test the role of PDGF-C and PDGF-D in the development and growth of undesired new blood vessels in the choroids and retina. Multiple approaches including different CNV mouse models, PDGF-C deficient and transgenic mice, neutralizing antibodies and siRNA, etc, will be used to achieve our scientific goals. Results derived from this study investigating the angiogenic nature of PDGF-C and PDGF-D in CNV formation and progression, as well as the anti-angiogenic effects of PDGF-C/D antagonists alone and in combination with other angiogenesis inhibitors will provide not only new insights into the basic molecular and cellular mechanisms of CNV formation in neovascular AMD, but also possibilities of novel therapy for the treatment of AMD patients.

Publications

Zhang, F., Tang, Z., Hou, X., Lennartsson, J., Li, Y., Koch, A. W., Scotney, P., Lee, C., Arjunan, P., Dong, L., Kumar, A., Rissanen, T. T. Wang, B., Nagai, N., Fons, P., Fariss, R., Zhang, Y., Wawrousek, E. Tansey, G., Raber, J., Fong, G. H., Ding, H., Greenberg, D. A., Becker, K. G., Herbert, J. M., Nash, A., Yla-Herttuala, S., Cao, Y., Watts, R. J. Li, X., (2009) VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis, PNAS, 106, 6152-6157  

Gavard, J., Hou, X., Qu, Y., Masedunskas, A., Martin, D., Weigert, R. Li, X., Gutkind, J. S., (2009) A Role for a CXCR2/PI3K{gamma} Signaling Axis in Acute and Chronic Vascular Permeability, Mol Cell Biol, 29, 2469-248?  

Xuri Li, Chunsik Lee, Zhongshu Tang, Fan Zhang, Pachiappan Arjunan, Yang Li, Xu Hou, Anil Kumar, Lijin Dong, (2009) VEGF-B: a survival, or an angiogenic factor?, Cell Adhesion &Migration, July, 2009 PMID: 19684473 [link not available] PDGF-CC blockade inhibits pathological angiogenesis by acting on multiple cellular and molecular targets Xu Houa,b, Anil Kumara, Chunsik Leea, Bin Wangc, Pachiappan Arjunana, Lijin Donga, Arvydas Maminishkisa, Zhongshu Tanga, Yang Lia, Fan Zhanga, Shi-Zhuang Zhangc, Piotr Wardegad, Sagarika Chakrabartya, Baoying Liua, Zhijian Wua, Peter Colosia, Robert N. Farissa, Johan Lennartssond, Robert Nussenblatta, J. Silvio Gutkinde, Yihai Caof, and Xuri Li  

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