Angiostatin inhibits and regresses corneal neovascularization

Balamurali K. Ambati, Antonia M. Joussen, Jayakrishna Ambati, Yasufumi Moromizato, Chandan Guha, Kashi Javaherian, Stephen Gillies, Michael S. O'Reilly, Anthony P. Adamis

Research output: Contribution to journalArticle

68 Scopus citations


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 nonangiostatin-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.

Original languageEnglish (US)
Pages (from-to)1063-1068
Number of pages6
JournalArchives of Ophthalmology
Issue number8
Publication statusPublished - Jan 1 2002


ASJC Scopus subject areas

  • Ophthalmology

Cite this

Ambati, B. K., Joussen, A. M., Ambati, J., Moromizato, Y., Guha, C., Javaherian, K., ... Adamis, A. P. (2002). Angiostatin inhibits and regresses corneal neovascularization. Archives of Ophthalmology, 120(8), 1063-1068.