April 1997
Volume 38, Issue 5
Free
Articles  |   April 1997
Inhibition of angiogenesis by tissue inhibitor of metalloproteinase-3.
Author Affiliations
  • B Anand-Apte
    Department of Surgical Research, Children's Hospital, Boston, Massachusetts, USA.
  • M S Pepper
    Department of Surgical Research, Children's Hospital, Boston, Massachusetts, USA.
  • E Voest
    Department of Surgical Research, Children's Hospital, Boston, Massachusetts, USA.
  • R Montesano
    Department of Surgical Research, Children's Hospital, Boston, Massachusetts, USA.
  • B Olsen
    Department of Surgical Research, Children's Hospital, Boston, Massachusetts, USA.
  • G Murphy
    Department of Surgical Research, Children's Hospital, Boston, Massachusetts, USA.
  • S S Apte
    Department of Surgical Research, Children's Hospital, Boston, Massachusetts, USA.
  • B Zetter
    Department of Surgical Research, Children's Hospital, Boston, Massachusetts, USA.
Investigative Ophthalmology & Visual Science April 1997, Vol.38, 817-823. doi:
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      B Anand-Apte, M S Pepper, E Voest, R Montesano, B Olsen, G Murphy, S S Apte, B Zetter; Inhibition of angiogenesis by tissue inhibitor of metalloproteinase-3.. Invest. Ophthalmol. Vis. Sci. 1997;38(5):817-823.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

PURPOSE: It has been established that Sorsby's fundus dystrophy, a dominantly inherited form of blindness, is caused by mutations in the tissue inhibitor of metalloproteinase-3 (TIMP-3) gene. Because choroidal neovascularization is a prominent feature of Sorsby's fundus dystrophy, the authors have examined whether TIMP-3 protein plays a role in the regulation of angiogenesis. METHODS: Chemotaxis of endothelial cells toward vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was examined using a modified Boyden chamber assay. Endothelial cells placed in the upper chamber were allowed to migrate through a polycarbonate membrane with 8 microns pores toward VEGF or bFGF present in the lower chamber. Next, the ability of TIMP-3 to inhibit chemotaxis was studied by incubating the cells with varying amounts of TIMP-3 during the assay. Finally, an in vitro angiogenesis assay was performed on collagen gels. Endothelial cells were seeded onto three-dimensional collagen gels. Treatment with bFGF and VEGF induced invasion of the gel and the formation of tube-like structures. TIMPs (1, 2, and 3) were added to the cultures to determine their effect on invasion. An in vivo chorioallantoic membrane (CAM) assay was performed using methylcellulose discs containing bFGF with or without TIMP-3. Induction of new blood vessels was observed with a stereomicroscope. RESULTS: TIMP-3 inhibits chemotaxis of vascular endothelial cells toward VEGF and bFGF, inhibits collagen gel invasion and capillary morphogenesis in vitro, and inhibits bFGF-induced angiogenesis in the CAM assay in vivo. CONCLUSIONS: TIMP-3 has the potential to inhibit angiogenesis. These results allow us to speculate on a possible mechanism by which mutant TIMP-3 protein might contribute to the Sorsby fundus dystrophy phenotype.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×