Inhibition of corneal neovascularization by blocking the angiotensin II type 1 receptor

Tomohiko Usui, Kenji Sugisaki, Aya Iriyama, Seiichi Yokoo, Satoru Yamagami, Norihiro Nagai, Susumu Ishida, Shiro Amano

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24 Citations (Scopus)

Abstract

PURPOSE. To determine the role of angiotensin II type 1 receptor (AT1R) signaling in corneal neovascularization. METHODS. Corneal neovascularization was induced by suturing 10-0 nylon 1 mm away from limbal vessels in C57 BJ6 mice. Angiotensinogen and its receptor (AT1R) gene expression levels were evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The expression of angiotensin II (Ang2) and AT1R was confirmed by Western blotting and immunohistochemistry. To investigate the function of Ang2 in corneal neovascularization, infiltrating macrophages in vascularized corneas and the neovascularized area were investigated after intraperitoneal injection of an AT1R antagonist (telmisartan, 10 mg/kg). Further, corneal mRNA of VEGF, MCP-1, IL-6, ICAM-1, and TNF-α was examined in control and telmisartan-treated mice. RESULTS. Ang2 and AT1R markedly increased in the neovascularized corneas compared with normal corneas. Ang2 and AT1R were expressed in epithelium and stromal cells (vascular endothelium, infiltrating leukocytes, and keratocytes) in neovascularized cornea at protein levels and were weakly detected in normal corneal epithelium. Infiltrating macrophages were reduced in telmisartan-treated mice on day 7 after suturing. Neovascularized area in the cornea of telmisartan-treated mice was 70% smaller than that of control mice on day 7 after suturing. A PPAR-γ antagonist partially, but significantly, reversed the suppressive effect of telmisartan on induction of corneal neovascularization. The expression of VEGF, MCP-1, IL-6, and ICAM-1 was significantly inhibited in telmisartantreated mice. CONCLUSIONS. These findings indicate that Ang2, abundantly expressed in neovascularized corneas, has a significant role in inflammation-related driven corneal neovascularization. AT1R may be a therapeutic target for the suppression of corneal neovascularization.

Original languageEnglish
Pages (from-to)4370-4376
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number10
DOIs
Publication statusPublished - 2008 Oct 1

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Usui, T., Sugisaki, K., Iriyama, A., Yokoo, S., Yamagami, S., Nagai, N., Ishida, S., & Amano, S. (2008). Inhibition of corneal neovascularization by blocking the angiotensin II type 1 receptor. Investigative Ophthalmology and Visual Science, 49(10), 4370-4376. https://doi.org/10.1167/iovs.07-0964