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NIH Research Festival

September 16 – 18, 2015

A new potential therapy for Age-Related Macular Degeneration (AMD): Anti-Angiogenic Activity of Fibulin-7 and its Fragments In Vivo

Wednesday, September 16, 2015 – Poster Session I
3:30 – 5:00 p.m.

FAES Terrace

NIDCR

MOLBIO-13

FARE Award Winner

Authors

  • T Ikeuchi
  • P Forcinito
  • S de Vega
  • J Amaral
  • I Rodrigez
  • E Arikawa-Hirasawa
  • Y Yamada

Abstract

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

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  • 2024
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    • NIH Early–Career Investigator Lectures
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