Angiostatin inhibits and regresses corneal neovascularization

Arch Ophthalmol. 2002 Aug;120(8):1063-8. doi: 10.1001/archopht.120.8.1063.


Objective: To determine the ability of angiostatin and the angiostatin-producing low-metastatic (LM) clone of Lewis lung carcinoma (LLC) to inhibit and regress corneal neovascularization, as compared with the non-angiostatin-producing high-metastatic (HM) clone.

Methods: Three groups of C57BL6/J mice underwent chemical and mechanical denudation of corneal and limbal epithelium. One group remained tumor free while the other 2 were implanted with LLC cells (either the HM or LM clones) subcutaneously the day before, 2 weeks after, or 4 weeks after denudation. Corneas were harvested 2 weeks after tumor implantation (at 2, 4, and 6 weeks after denudation for tumor-free mice). Neovascularization was quantified by CD31 immunostaining. In a second experiment, recombinant angiostatin was delivered continuously for 2 weeks via an osmotic pump in mice with established corneal neovascularization.

Results: The mean percentages of neovascularized corneal area in mice 2 weeks after LM-LLC implantation were 4.6%, 3.7%, and 37.0%, at 2, 4, and 6 weeks after scraping, respectively. In contrast, in the mice implanted with HM-LLC, the corresponding values were 45.4% (P =.01), 90.1% (P =.03), and 80.3% (P =.005). For tumor-free mice, the corresponding values were 62.0% (P =.003), 68.9% (P =.03), and 59.3% (P =.06). Mice implanted with angiostatin pumps had a 37.7% neovascularized corneal area 2 weeks after implantation and 4 weeks after scraping while mice implanted with sham pumps had 60.5% (P =.007).

Conclusion: Angiostatin inhibits and regresses corneal neovascularization induced by mechanical and alkali corneal injury.

Clinical relevance: This appears to be the first evidence of biologically induced regression of corneal neovascularization, and the first direct demonstration of angiostatin-induced regression of neovascularization in any tissue.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / metabolism
  • Angiogenesis Inhibitors / therapeutic use*
  • Angiostatins
  • Animals
  • Carcinoma, Lewis Lung / metabolism
  • Cornea / blood supply
  • Cornea / drug effects
  • Cornea / pathology
  • Corneal Neovascularization / drug therapy*
  • Corneal Neovascularization / metabolism
  • Corneal Neovascularization / pathology
  • Fluorophotometry
  • Infusion Pumps, Implantable
  • Lung Neoplasms / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Peptide Fragments / metabolism
  • Peptide Fragments / therapeutic use*
  • Plasminogen / metabolism
  • Plasminogen / therapeutic use*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Recombinant Proteins


  • Angiogenesis Inhibitors
  • Peptide Fragments
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Recombinant Proteins
  • Angiostatins
  • Plasminogen