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N. Nagai, Y. Oike, K. Izumi, T. Urano, Y. Kubota, Y. Ozawa, M. Inoue, K. Tsubota, T. Suda, S. Ishida; Angniotension II Type 1 Receptor–Mediated Inflammation Is Required for Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2006;47(13):903.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the role of the rein–angiotensin system (RAS) in the development of choroidal neovasculariztion (CNV).
Laser photocoagulation was used to induce CNV in C57BL/6 mice. Tissue localization of angiotensin II type 1 receptor (AT1–R) in CNV tissues of laser–treated mice and of patients with age–related macular degeneration (AMD) was analyzed by immunohistochemistry. mRNA and protein levels of AT1–R and AT2–R in the choroid of laser–treated mice were examined by RT–PCR and western blot analyses, respectively. An AT1–R blocker (ARB, telmisartan or valsartan) or an AT2–R blocker was administered daily for 1 week before and after the photocoagulation. One week after the photocoagulation, CNV volume was evaluated by volumetric measurements. Macrophages infiltrating to murine CNV were identified by immunostainig for F4/80. Choroidal mRNA and protein levels of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)–1, VEGFR–2, intercellular adhesion molecule (ICAM)–1, monocyte chemotactic protein (MCP)–1 and interleukin (IL)–6 were examined by RT–PCR and ELISA, respectively.
AT1–R immunoreactivity was detected in vascular endothelial cells and infiltrating macrophages in human and murine CNV tissues. Induction of CNV led to an increase in choroidal mRNA and protein levels of AT1–R, but not AT2–R. CNV volume was significantly suppressed by the treatment with an AT1–R blocker (telmisartan or valsartan), but not with an AT2–R blocker. AT1–R blockade by telmisartan significantly suppressed macrophage infiltration and choroidal VEGFR–1, ICAM–1, MCP–1 and IL–6 levels compared to the vehicle treatment.
AT1–R signaling blockade inhibited various inflammatory processes such as choroidal ICAM–1, MCP–1 and IL–6 upregulation and macrophage infiltration, resulting in the suppression of CNV. The present data indicate the possibility of AT1–R blockade as a novel therapeutic strategy to inhibit CNV associated with AMD.
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