HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response View responses Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Nagai, N. Articles by Ishida, S. Search for Related Content PubMed PubMed Citation Articles by Nagai, N. Articles by Ishida, S.

Selective Suppression of Pathologic, but Not Physiologic, Retinal Neovascularization by Blocking the Angiotensin II Type 1 Receptor

¹From the Departments of Ophthalmology, ²Cell Differentiation, and ³Pathology, Keio University School of Medicine, Tokyo, Japan.

PURPOSE. To investigate the anti-inflammatory and anti-angiogenic effects of telmisartan, an angiotensin II type 1 receptor (AT1-R) antagonist, on ischemia-induced retinal neovascularization.

METHODS. C57BL/6 neonatal mice were reared in an 80% concentration of oxygen from postnatal day (P)7 to P12, followed by room-air breathing until P17, to induce ischemia-initiated retinal neovascularization (i.e., a murine model of ischemic retinopathy). Tissue localization of AT1-R was examined by immunohistochemistry for murine retinal wholemounts and human fibrovascular tissues excised at vitrectomy for proliferative diabetic retinopathy. Animals received intraperitoneal injection of telmisartan or vehicle. A concanavalin A lectin perfusion-labeling technique was used to evaluate the areas of physiological and pathologic retinal new vessels and the number of leukocytes adhering to the vasculature. Retinal mRNA and protein levels of intercellular adhesion molecule (ICAM)-1, vascular endothelial growth factor receptor (VEGFR)-1, and VEGFR-2 were examined by RT-PCR and ELISA.

RESULTS. Vessels in human fibrovascular tissues and the murine retinas were positive for AT1-R. Pathologic (P < 0.01), but not physiologic (P > 0.05), retinal neovascularization was significantly suppressed in telmisartan-treated mice compared with vehicle-treated animals. The number of adherent leukocytes (P < 0.01) was also significantly reduced, together with retinal ICAM-1 levels (P < 0.01) in the telmisartan-treated group compared with the control group. No significant difference was detected in retinal VEGFR-2 levels between the two groups, whereas retinal VEGFR-1 levels in the telmisartan-treated group were significantly (P < 0.05) lower than in the vehicle-treated group.

CONCLUSIONS. The present findings suggest that the AT1-R signaling blockade leads to the selective suppression of pathologic, but not physiological, retinal neovascularization through the inhibition of the inflammatory processes related to pathologic neovascularization.

This article has been cited by other articles:

				N. Nagai, K. Izumi-Nagai, Y. Oike, T. Koto, S. Satofuka, Y. Ozawa, K. Yamashiro, M. Inoue, K. Tsubota, K. Umezawa, et al. Suppression of Diabetes-Induced Retinal Inflammation by Blocking the Angiotensin II Type 1 Receptor or Its Downstream Nuclear Factor-{kappa}B Pathway Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4342 - 4350. [Abstract] [Full Text] [PDF]

				P. deS. Senanayake, J. Drazba, K. Shadrach, A. Milsted, E. Rungger-Brandle, K. Nishiyama, S.-I. Miura, S. Karnik, J. E. Sears, and J. G. Hollyfield Angiotensin II and Its Receptor Subtypes in the Human Retina Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3301 - 3311. [Abstract] [Full Text] [PDF]

				J. Herrmann and A. Lerman Atherosclerosis in the Back Yard J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2102 - 2104. [Abstract] [Full Text] [PDF]

				N. Nagai, Y. Oike, K. Izumi-Nagai, T. Koto, S. Satofuka, H. Shinoda, K. Noda, Y. Ozawa, M. Inoue, K. Tsubota, et al. Suppression of Choroidal Neovascularization by Inhibiting Angiotensin-Converting Enzyme: Minimal Role of Bradykinin Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2321 - 2326. [Abstract] [Full Text] [PDF]

				S. Satofuka, A. Ichihara, N. Nagai, T. Koto, H. Shinoda, K. Noda, Y. Ozawa, M. Inoue, K. Tsubota, H. Itoh, et al. Role of Nonproteolytically Activated Prorenin in Pathologic, but Not Physiologic, Retinal Neovascularization Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 422 - 429. [Abstract] [Full Text] [PDF]

				N. Nagai, Y. Oike, K. Izumi-Nagai, T. Urano, Y. Kubota, K. Noda, Y. Ozawa, M. Inoue, K. Tsubota, T. Suda, et al. Angiotensin II Type 1 Receptor-Mediated Inflammation Is Required for Choroidal Neovascularization Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2252 - 2259. [Abstract] [Full Text] [PDF]

				L. Hunyady and K. J. Catt Pleiotropic AT1 Receptor Signaling Pathways Mediating Physiological and Pathogenic Actions of Angiotensin II Mol. Endocrinol., May 1, 2006; 20(5): 953 - 970. [Abstract] [Full Text] [PDF]

				N. Nagai, Y. Oike, K. Noda, T. Urano, Y. Kubota, Y. Ozawa, H. Shinoda, T. Koto, K. Shinoda, M. Inoue, et al. Suppression of Ocular Inflammation in Endotoxin-Induced Uveitis by Blocking the Angiotensin II Type 1 Receptor Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2925 - 2931. [Abstract] [Full Text] [PDF]

eLetters: