April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
(Pro)renin Receptor-Mediated Signal Transduction and Tissue Renin-Angiotensin System Contribute to Diabetes-Induced Retinal Inflammation
S. Satofuka; A. Ichihara; N. Nagai; K. Noda; Y. Ozawa; A. Fukamizu; K. Tsubota; H. Itoh; Y. Oike; S. Ishida
Author Affiliations & Notes
  • S. Satofuka
    Laboratory of Retinal Cell Biology,
    Department of Ophthalmology,
    Keio University School of Medicine, Tokyo, Japan
  • A. Ichihara
    Department of Internal Medicine,
    Keio University School of Medicine, Tokyo, Japan
  • N. Nagai
    Laboratory of Retinal Cell Biology,
    Department of Ophthalmology,
    Keio University School of Medicine, Tokyo, Japan
  • K. Noda
    Laboratory of Retinal Cell Biology,
    Department of Ophthalmology,
    Keio University School of Medicine, Tokyo, Japan
  • Y. Ozawa
    Laboratory of Retinal Cell Biology,
    Department of Ophthalmology,
    Keio University School of Medicine, Tokyo, Japan
  • A. Fukamizu
    Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan
  • K. Tsubota
    Department of Ophthalmology,
    Keio University School of Medicine, Tokyo, Japan
  • H. Itoh
    Department of Internal Medicine,
    Keio University School of Medicine, Tokyo, Japan
  • Y. Oike
    Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
  • S. Ishida
    Laboratory of Retinal Cell Biology,
    Department of Ophthalmology and Inaida Endowed Department of Anti-Aging Ophthalmology,
    Keio University School of Medicine, Tokyo, Japan
  • Footnotes
    Commercial Relationships  S. Satofuka, None; A. Ichihara, None; N. Nagai, None; K. Noda, None; Y. Ozawa, None; A. Fukamizu, None; K. Tsubota, None; H. Itoh, None; Y. Oike, None; S. Ishida, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5380. doi:
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      S. Satofuka, A. Ichihara, N. Nagai, K. Noda, Y. Ozawa, A. Fukamizu, K. Tsubota, H. Itoh, Y. Oike, S. Ishida; (Pro)renin Receptor-Mediated Signal Transduction and Tissue Renin-Angiotensin System Contribute to Diabetes-Induced Retinal Inflammation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5380.

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Abstract

Purpose: : Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanisms whereby prorenin binding to its receptor dually activates tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling via the receptor. The aim of the present study was to define the association of RAPS with diabetes-induced retinal inflammation.

Methods: : Long-Evans rats, C57BL/6 mice or angiotensin II type 1 receptor (AT1-R)-deficient mice with streptozotocin-induced diabetes were treated with (pro)renin receptor blocker (PRRB). Retinal mRNA expression of prorenin and (pro)renin receptor was examined by quantitative RT-PCR. Leukocyte adhesion to the retinal vasculature was evaluated with a concanavalin A lectin perfusion-labeling technique. Retinal protein levels of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM)-1 were examined by ELISA. Retinal ERK activation was analyzed by western blotting.

Results: : Induction of diabetes led to significant increase in retinal expression of prorenin, but not (pro)renin receptor. Retinal adherent leukocytes were significantly suppressed with PRRB. Administration of PRRB inhibited diabetes-induced retinal expression of VEGF and ICAM-1. To clarify the role of signal transduction via (pro)renin receptor in the diabetic retina, we utilized AT1-R-deficient mice in which RAS was deactivated. Retinal adherent leukocytes in AT1-R-deficient diabetic mice were significantly suppressed with PRRB. PRRB suppressed the activation of ERK and the production of VEGF, but not ICAM-1, in AT1-R-deficient diabetic mice.

Conclusions: : These results indicate significant contribution of RAPS to the pathogenesis of diabetes-induced retinal inflammation, suggesting the possibility of (pro)renin receptor as a novel, molecular target for the treatment of diabetic retinopathy.

Keywords: diabetic retinopathy • inflammation • vascular endothelial growth factor 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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