title: Angiotensin II type 1 receptor-mediated inflammation is required for choroidal neovascularization.
abstract: BACKGROUND
  Choroidal neovascularization (CNV) is a critical pathogenesis in age-related macular degeneration, the most common cause of blindness in the developed countries. The aim of the current study was to determine the involvement of the renin-angiotensin system (RAS) with the development of CNV, using human surgical samples and the murine model of laser-induced CNV.
  
  
  RESULTS
  In the human and murine CNV tissues, the vascular endothelium expressed angiotensin II type 1 receptor (AT1-R), AT2-R, and angiotensin II. The CNV volume was significantly suppressed by treatment with an AT1-R blocker telmisartan, but not with an AT2-R blocker. AT1-R signaling blockade with telmisartan inhibited various inflammatory mechanisms including macrophage infiltration and upregulation of VEGF, intercellular adhesion molecule-1 (ICAM-1), MCP-1, and IL-6 in the retinal pigment epithelium-choroid complex. A PPAR-gamma antagonist partially but significantly reversed the suppressive effect of telmisartan on in vivo induction of CNV and in vitro upregulation of ICAM-1 and MCP-1 in endothelial cells and IL-6 in macrophages, showing the dual contribution of PPAR-gamma-agonistic and AT1-R-antagonistic actions in the telmisartan treatment.
  
  
  CONCLUSIONS
  AT1-R-mediated inflammation plays a pivotal role in the development of CNV, indicating the possibility of AT1-R blockade as a novel therapeutic strategy to inhibit CNV.
authors.affiliation: Laboratory of Retinal Cell Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nagai
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Kanako
authors.initials: K
authors.lastname: Izumi-Nagai
authors.forename: Takashi
authors.initials: T
authors.lastname: Urano
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kubota
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000209:etiology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D000077333:Telmisartan; D014018:Tissue Distribution
chemical_list: D043925:Angiogenesis Inducing Agents; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D018836:Inflammation Mediators; D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D000077333:Telmisartan