NIH Research Festival
FARE Award Winner
AMD is the leading cause of blindness in patients older than 50 years. The blindness is caused by abnormal angiogenesis of the choroidal vasculature via Brunch’s membrane. Fibulin-7 (Fbln7) is a newly discovered member of the extracellular fibulin family proteins, functioning as a cell adhesion molecule and interacting with other ECM proteins and receptors. Fbln7 is expressed in retinal pigment epithelium cells as well as choroidal capillary walls. Using a recombinant protein approach, we previously showed that the C-terminal Fbln7 fragment (Fbln7-C) inhibits tube formation of human umbilical vein endothelial cells (HUVEC) in cultures and blocks vessel sprouting in aortic ring assays in vitro. In this study, we hypothesize that Fbln7-C has anti-angiogenic properties in vivo and could be a potential therapeutic compound for angiogenesis. We studied anti-angiogenic activity of full-length Fbln7 (Fbln7-FL) and Fbln7-C in vivo using a rat corneal model. The implant with pro-angiogenic lipid 7-ketocholesterol (7KCh) alone started to induce neovascularization from the limbus. The 7KCh implants containing Fbln7-FL or Fbln7-C inhibited neovascularization in a dose-dependent manner. We are also studying the mechanism of the anti-angiogenic activity of Fbln7-C. Our preliminary data showed that Fbln7-C bound to the vascular endothelial growth factor receptor (VEGFR), suggesting that inhibition of VEGF signaling is involved in Fbln7-mediated anti-angiogenic activity. We will further study how the interaction affects endothelial cell, migration, proliferation, and differentiation.
Scientific Focus Area: Molecular Biology and Biochemistry
This page was last updated on Friday, March 26, 2021