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Table of Contents
Vol. 39, No. 2, 2007
Issue release date: March 2007
Section title: Original Paper
Ophthalmic Res 2007;39:92–97
(DOI:10.1159/000099244)

Pigment-Epithelium-Derived Factor Suppresses Expression of Receptor for Advanced Glycation End Products in the Eye of Diabetic Rats

Yamagishi S.a · Matsui T.a · Nakamura K.a · Yoshida T.a · Takeuchi M.c · Inoue H.b · Yoshida Y.a · Imaizumi T.a
aDepartment of Internal Medicine and bRadioisotope Institute for Basic and Clinical Medicine, Kurume University School of Medicine, Kurume, and cDepartment of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa, Japan

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 28, 2006
Accepted: November 10, 2006
Published online: February 02, 2007
Issue release date: March 2007

Number of Print Pages: 6
Number of Figures: 2
Number of Tables: 0

ISSN: 0030-3747 (Print)
eISSN: 1423-0259 (Online)

For additional information: http://www.karger.com/ORE

Abstract

The interaction of advanced glycation end products (AGEs) and their receptor (RAGE) elicits inflammatory and proliferative responses in retinal vascular wall cells, thereby being involved in the pathogenesis of diabetic retinopathy. Recently, pigment-epithelium-derived factor (PEDF) has also been shown to play a role in diabetic retinopathy. However, the effects of PEDF on RAGE gene expression remain to be elucidated. Therefore, we investigated here whether PEDF could prevent diabetes- or AGE-induced RAGE gene expression and the way that it might achieve this effect. Administration of PEDF or pyridoxal phosphate, an AGE inhibitor, suppressed RAGE gene expression in the eye of streptozotocin-induced diabetic rats. Further, intravenous injection of AGEs to normal rats increased RAGE gene expression, which was also blocked by PEDF. In vitro, PEDF or an antioxidant N-acetylcysteine blocked the AGE-induced RAGE gene induction in microvascular endothelial cells. In addition, PEDF completely inhibited superoxide generation and NF-ĸB activation in AGE-exposed endothelial cells. These results demonstrated that PEDF could inhibit diabetes- or AGE-induced RAGE gene expression by blocking the superoxide-mediated NF-ĸB activation. Our present study suggests that pharmacological upregulation or substitution of PEDF may play a protective role against diabetic retinopathy by attenuating the deleterious effect of AGEs.

© 2007 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 28, 2006
Accepted: November 10, 2006
Published online: February 02, 2007
Issue release date: March 2007

Number of Print Pages: 6
Number of Figures: 2
Number of Tables: 0

ISSN: 0030-3747 (Print)
eISSN: 1423-0259 (Online)

For additional information: http://www.karger.com/ORE


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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