Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization

Vincent Lambert, Carine Munaut, Agnès Noël, Francis Frankenne, Khalid Bajou, Robert Gerard, Peter Carmeliet, Marie Paule Defresne, Jean Michel Foidart, Jean Marie Rakic

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

High levels of the plasminogen activators, but also their inhibitor, plasminogen activator inhibitor 1 (PAI-1), have been documented in neovascularization of severe ocular pathologies such as diabetic retinopathy or age-related macular degeneration (AMD). AMD is the primary cause of irreversible photoreceptors loss, and current therapies are limited. PAI-1 has recently been shown to be essential for tumoral angiogenesis. We report here that deficient PAI-1 expression in mice prevented the development of subretinal choroidal angiogenesis induced by laser photocoagulation. When systemic and local PAI-1 expression was achieved by intravenous injection of a replication-defective adenoviral vector expressing human PAI-1 cDNA, the wild-type pattern of choroidal angiogenesis was restored. These observations demonstrate the proangiogenic activity of PAI-1 not only in tumoral models, but also in choroidal experimental neovascularization sharing similarities with human AMD. They identify therefore PAI-1 as a potential target for therapeutic ocular anti-angiogenic strategies.

Original languageEnglish (US)
Pages (from-to)1021-1027
Number of pages7
JournalFASEB Journal
Volume15
Issue number6
DOIs
StatePublished - 2001

Keywords

  • Angiogenesis
  • Macular degeneration
  • Proteases
  • Retinal disease
  • Viral vector

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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