Angiostatin inhibits and regresses corneal neovascularization.

Abstract

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.

• Authors: Balamurali K Ambati, Antonia M Joussen, Jayakrishna Ambati, Yasufumi Moromizato, Chandan Guha, Kashi Javaherian, Stephen Gillies, Michael S O'Reilly, Anthony P Adamis
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 120 Issue 8 Pg. 1063-8 (Aug 2002) ISSN: 0003-9950 [Print] United States
• PMID: 12149060 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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