Inhibition of retinal neovascularization by intraocular viral-mediated delivery of anti-angiogenic agents

Mol Ther. 2002 Oct;6(4):490-4. doi: 10.1006/mthe.2002.0702.

Abstract

Neovascularization characterizes diabetic retinopathy and choroidal neovascularization associated with age-related macular degeneration, the most common causes of severe visual loss in the developed world. Gene transfer to the eye using adeno-associated viral (AAV) vectors is a promising new treatment for inherited and acquired ocular diseases. We used an AAV vector with rapid onset and high levels of gene expression in the retina to deliver three anti-angiogenic factors (pigment epithelium-derived factor, tissue inhibitor of metalloproteinase-3, and endostatin) to the eyes of mice in a mouse model of retinopathy of prematurity. All three vectors inhibited ischemia-induced neovascularization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / genetics
  • Angiogenesis Inhibitors / pharmacology*
  • Collagen / genetics
  • Collagen / pharmacology*
  • Cytomegalovirus / genetics
  • Dependovirus / genetics
  • Endostatins
  • Endothelium, Vascular / metabolism
  • Eye Proteins*
  • Gene Transfer Techniques*
  • Genes, Reporter
  • Genetic Vectors
  • Humans
  • In Vitro Techniques
  • Nerve Growth Factors*
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology*
  • Promoter Regions, Genetic
  • Proteins / genetics
  • Retinal Neovascularization / drug therapy*
  • Serpins / genetics
  • Tissue Inhibitor of Metalloproteinase-3
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Transduction, Genetic

Substances

  • Angiogenesis Inhibitors
  • Endostatins
  • Eye Proteins
  • Nerve Growth Factors
  • Peptide Fragments
  • Proteins
  • Serpins
  • TIMP3 protein, human
  • Tissue Inhibitor of Metalloproteinase-3
  • Tissue Inhibitor of Metalloproteinases
  • pigment epithelium-derived factor
  • Collagen