| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Laboratory of Retinal Cell Biology and the 2Departments of Ophthalmology, 3Internal Medicine, and 4Cell Differentiation, Keio University School of Medicine, Tokyo, Japan.
PURPOSE. Recently, it was revealed that the inhibition of nonproteolytic activation of prorenin led to significant suppression of ocular inflammation in endotoxin-induced uveitis. The purpose of the present study was to investigate whether nonproteolytically activated prorenin plays a role in ischemia-induced retinal neovascularization.
METHODS. C57BL/6 neonatal mice were reared in an 80% concentration of oxygen from postnatal (P) day 7 to P12, followed by room-air breathing to P17 to induce ischemia-initiated retinal neovascularization. Tissue localization of activated prorenin and prorenin receptor was examined by immunohistochemistry. Animals received intraperitoneal injections of handle-region peptide (HRP), a decoy peptide corresponding to the handle region of prorenin, which inhibits prorenin receptor-mediated upregulation of the renin-angiotensin system (RAS). A concanavalin A lectin perfusion-labeling technique was used to evaluate the areas of physiologic and pathologic retinal new vessels and the number of leukocytes adhering to the vasculature. Retinal mRNA expression and protein levels of intercellular adhesion molecule (ICAM)-1, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1, and VEGFR-2 were examined by RT-PCR and ELISA.
RESULTS. Retinal vessels in ischemic retinopathy eyes were positive for activated prorenin and prorenin receptor. Pathologic, but not physiologic, retinal neovascularization was significantly attenuated in HRP-treated mice compared with vehicle- or control peptide-treated animals. The number of adherent leukocytes was also significantly reduced. Retinal mRNA expression and protein levels of ICAM-1, VEGF, VEGFR-1, and VEGFR-2 in ischemic retinopathy were also significantly suppressed by the application of HRP.
CONCLUSIONS. The present findings suggest that nonproteolytic activation of prorenin selectively promotes pathologic, but not physiologic, retinal neovascularization through the inflammatory processes related to pathologic neovascularization.
This article has been cited by other articles:
|
|
 |
|
  J. L. Wilkinson-Berka and D. J. Campbell (Pro)renin Receptor: A Treatment Target for Diabetic Retinopathy? Diabetes, July 1, 2009; 58(7): 1485 - 1487. [Full Text] [PDF]
|
|
|
|
|
|
S. Satofuka, A. Ichihara, N. Nagai, K. Noda, Y. Ozawa, A. Fukamizu, K. Tsubota, H. Itoh, Y. Oike, and S. Ishida (Pro)renin Receptor-Mediated Signal Transduction and Tissue Renin-Angiotensin System Contribute to Diabetes-Induced Retinal Inflammation Diabetes, July 1, 2009; 58(7): 1625 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Wilkinson-Berka Prorenin and the (Pro)renin Receptor in Ocular Pathology Am. J. Pathol., December 1, 2008; 173(6): 1591 - 1594. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Satofuka, A. Ichihara, N. Nagai, K. Noda, Y. Ozawa, A. Fukamizu, K. Tsubota, H. Itoh, Y. Oike, and S. Ishida (Pro)renin Receptor Promotes Choroidal Neovascularization by Activating Its Signal Transduction and Tissue Renin-Angiotensin System Am. J. Pathol., December 1, 2008; 173(6): 1911 - 1918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Danser and G. Nguyen Spotlight on Renin: The Renin Academy Summit: advancing the understanding of renin science Journal of Renin-Angiotensin-Aldosterone System, June 1, 2008; 9(2): 119 - 123. [PDF]
|
|
|
|
 |
|
 Z. Shan, A. E. Cuadra, C. Sumners, and M. K. Raizada Characterization of a functional (pro)renin receptor in rat brain neurons Exp Physiol, May 1, 2008; 93(5): 701 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Nguyen and A. H. J. Danser Prorenin and (pro)renin receptor: a review of available data from in vitro studies and experimental models in rodents Exp Physiol, May 1, 2008; 93(5): 557 - 563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Campbell Critical Review of Prorenin and (Pro)renin Receptor Research Hypertension, May 1, 2008; 51(5): 1259 - 1264. [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
