Pathways Regulating Angiogenesis in Epithelial Cells
Principal Investigator
Project Summary
Bruch's membrane is a layer of retinal tissue upon which the retinal pigment epithelium (RPE) lies. Just below Bruch's membrane is the choroid layer, a region containing many blood vessels and capillaries. The increased growth of new capillaries in the choroid layer (as seen in wet macular degeneration) is initiated through the action of growth factors on endothelial cells, which are the building blocks of capillaries. Vascular endothelial growth factor (VEGF) has been identified as the principal agent responsible for new capillary growth (angiogenesis) in the body. But it is also known that other growth factors can participate in the progression of ocular neovascularization. These factors have been identified as bFGF, TGFß, PDGF and IGF-1. So far, there is little information on the role that IGF-1 plays in neovascularization, but Dr. Rosenzweig has shown that IGF-1 stimulates the secretion of VEGF by RPE cells in culture. He is now studying how VEGF secretion is regulated in human RPE cells in tissue culture by treating them with IGF-1 or hypoxic conditions. This study could lead to the identification of new drug targets for the inhibition of choroidal neovascularization in age- related macular degeneration..
Publications
Slomiany, M.G. and Rosenzweg, S.A. (2006) Hypoxia-inducible factor-1-dependent and -independent regulation of insulin-like growth factor-1-stimulated vascular endothelial growth factor secretion. J Pharmacol Exp Ther. 318(2):666-75. Epub 2006 May 8. 
Slomiany, M.G., Black, L.A., Kibbey, M.M., Day, T.A., and Rosenzweig, S.A. (2006) IGF-1 induced vascular endothelial growth factor secretion in head and neck squamous cell carcinoma. Biochem Biophys Res Commun. 342(3):851-858. Epub 2006 Feb 20.
[Book Chapter] Slomiany, M.G. and Rosenzweg, S.A (2005) Insulin-like growth factor-1 and its binding proteins. Regulation and Secretion and mechanism of action. In: The somatotrophic axis in brain function: Current knowledge on growth hormone and insulin-like growth factors and their role in the central nervous system. F. Nyberg, ed., Elsevier Press, Amsterdam Slomiany, M.G. and Rosenzweig, S.A. (2004) IGF-1- induced VEGF and IGFBP-3 secretion correlates with increased HIF-1 alpha expression and activity in retinal pigment epithelial cell line D407. Invest. Ophthalmology. Vis Sci. 45(8):2838-2847.
Slomiany, M.G. and Rosenzweig, S.A. (2004) Autocrine effects of IGF-1 induced VEGF and IGFBP-3 secretion in retinal pigment epithelial cell line ARPE-19. Am J Physiol Cell Physiol. 2004 Sep;287(3):C746-53
First published on: June 11, 2008
Last modified on: December 22, 2024