A single local injection of recombinant VEGF receptor 2 but not of Tie2 inhibits retinal neovascularization in the mouse

Curr Eye Res. 2005 Apr;30(4):249-57. doi: 10.1080/02713680590923249.

Abstract

Purpose: The purpose of this study was to develop pharmacological therapeutic alternatives for ischemia-induced proliferative retinopathy.

Methods: C57BL/6J mice were placed in 76% oxygen on postnatal day 7 (P7) for 5 days. On P12 recombinant, chimeric vascular endothelial growth factor (sVEGF-R2) or sTie2 was injected intravitreally in one eye. The fellow eye received a control injection. On P17, retinal wholemounts were prepared after perfusion with fluorescein-dextran to quantify the retinopathy.

Results: A single intravitreal injection of sVEGF-R2 reduced pathologic vascular changes significantly (p = 0.02). No significant effect was observed after intravitreal application of sTie2 (p = 0.07), although Ang-2 was upregulated in control animals without treatment as neovascularization developed and Ang-1 was constantly transcribed (ratio PCR).

Conclusions: sVEGF-R2 interferes with VEGF signaling via VEGF-R2 receptor. Thus, local application of soluble receptors for angiogenic factors is a possible therapy for proliferative retinopathy. Receptors with a wide range of ligands might prove more useful for local application than those binding few or antagonistic ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1 / analogs & derivatives*
  • Angiopoietin-1 / genetics
  • Angiopoietin-1 / metabolism
  • Angiopoietin-2 / genetics
  • Angiopoietin-2 / metabolism
  • Animals
  • Dextrans
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescein Angiography
  • Fluoresceins
  • Injections
  • Mice
  • Mice, Inbred C57BL
  • Oxygen / toxicity
  • RNA, Messenger / metabolism
  • Receptor, TIE-2 / administration & dosage*
  • Receptor, TIE-2 / metabolism
  • Receptors, Fc
  • Recombinant Fusion Proteins
  • Retinal Neovascularization / chemically induced
  • Retinal Neovascularization / pathology
  • Retinal Neovascularization / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • Vascular Endothelial Growth Factor Receptor-2 / administration & dosage*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Vitreous Body

Substances

  • Angiopoietin-1
  • Angiopoietin-2
  • Angpt1 protein, mouse
  • Dextrans
  • Fluoresceins
  • RNA, Messenger
  • Receptors, Fc
  • Recombinant Fusion Proteins
  • fluorescein-dextran
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor Receptor-2
  • Oxygen