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      Detection of PEDF in Subretinal Fluid of Retinal Detachment: Possible Role in the Prevention of Subretinal Neovascularization

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          Abstract

          PEDF (pigment-epithelium-derived factor) is a member of the serpin family of protease inhibitors. It is considered to be an important regulator of human eye disease and is known to inhibit angiogenesis. We have therefore investigated the presence of PEDF in the subretinal fluid of patients with retinal detachment. Methods: Eighteen samples from SRF were collected from patients during retinal detachment surgery. Specific ELISA analysis was performed with specific IgG against human PEDF. Results: PEDF was detected in the subretinal fluid of all cases. The mean concentration of PEDF was 33.9 ng/ml (SD 23.7 ng/ml; range 5.3–74.7 ng/ml). The majority of samples had however a concentration of more than 22 ng PEDF/ml fluid. Conclusion: PEDF appears to be a constant component of the fluid accumulating in the subretinal space after retinal detachment. The known effects of PEDF, however, suggest that it may be involved in physiological processes of wound healing in the subretinal space.

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          Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor.

          Mohammad Amin Shaygan, Hong-Wei Zhou, F Stuart … (2002)
          Natural inhibitors of angiogenesis are able to block pathological neovascularization without harming the preexisting vasculature. Here we show that two such inhibitors, thrombospondin-1 and pigment epithelium-derived factor, derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (FasL)-mediated apoptosis to block angiogenesis. Both inhibitors upregulated FasL on endothelial cells. Expression of the essential partner of FasL, Fas/CD95 receptor, was low on quiescent endothelial cells and vessels but greatly enhanced by inducers of angiogenesis, thereby specifically sensitizing the stimulated cells to apoptosis by inhibitor-generated FasL. The anti-angiogenic activity of thrombospondin-1 and pigment epithelium-derived factor both in vitro and in vivo was dependent on this dual induction of Fas and FasL and the resulting apoptosis. This example of cooperation between pro- and anti-angiogenic factors in the inhibition of angiogenesis provides one explanation for the ability of inhibitors to select remodeling capillaries for destruction.
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            Pigment epithelium-derived factor inhibits retinal and choroidal neovascularization.

            A Ando, Lai Wei, Lynelle Takahashi … (2001)
            In this study, we investigated whether overexpression of pigment epithelium-derived factor (PEDF) by gene transfer can inhibit neovascularization by testing its effect in three different models of ocular neovascularization. Intravitreous injection of an adenoviral vector encoding PEDF resulted in expression of PEDF mRNA in the eye measured by RT-PCR and increased immunohistochemical staining for PEDF protein throughout the retina. In mice with laser-induced rupture of Bruch's membrane, choroidal neovascularization was significantly reduced after intravitreous injection of PEDF vector compared to injection of null vector or no injection. Subretinal injection of the PEDF vector resulted in prominent staining for PEDF in retinal pigmented epithelial cells and strong inhibition of choroidal neovascularization. In two models of retinal neovascularization (transgenic mice with increased expression of vascular endothelial growth factor (VEGF) in photoreceptors and mice with oxygen-induced ischemic retinopathy), intravitreous injection of null vector resulted in decreased neovascularization compared to no injection, but intravitreous injection of PEDF vector resulted in further inhibition of neovascularization that was statistically significant. These data suggest that sustained increased intraocular expression of PEDF by gene therapy might provide a promising approach for treatment of ocular neovascularization. Copyright 2001 Wiley-Liss, Inc.
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              Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy.

              M Matsumura, N Ogata, M Matsuoka … (2004)
              To determine whether pigment epithelium derived factor (PEDF), a protein that inhibits angiogenesis, is expressed in human choroidal neovascular membranes (CNVMs) and in tissues from an eye with polypoidal choroidal vasculopathy (PCV). In addition, to compare the expression of PEDF with that of vascular endothelial growth factor (VEGF), a known stimulator of angiogenesis, in these tissues. CNVMs, associated with age related macular degeneration (AMD), angioid streaks, and PCV, were obtained during surgery. The expression of PEDF and VEGF in the excised subretinal fibrovascular membranes was determined by immunohistochemistry. PEDF and VEGF were strongly expressed in the vascular endothelial cells and retinal pigment epithelial (RPE) cells in the CNVMs where numerous new vessels were prominent (clinically active CNVMs). On the other hand, immunoreactivity for PEDF and VEGF was weak in the new vessels where fibrosis was prominent (clinically quiescent CNVMs). However, the RPE cells were still positive for PEDF and VEGF. The specimens from the eye with PCV also showed strong expression of PEDF and VEGF in the vascular endothelial cells and the RPE cells. Because PEDF is an inhibitor of ocular angiogenesis and an inhibitor of ocular cell proliferation, our results suggest that PEDF along with VEGF may modulate the formation of subfoveal fibrovascular membranes.
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                Author and article information

                Journal
                Journal ID (publisher-id): ORE
                Journal ID (nlm-ta): Ophthalmic Res
                Journal ID (doi): 10.1159/issn.0030-3747
                Title: Ophthalmic Research
                Publisher: S. Karger AG
                ISSN (Print): 0030-3747
                ISSN (Electronic): 1423-0259
                Publication date Subscription-year: 2006
                Publication date (Print): August 2006
                Publication date (Electronic): 10 August 2006
                Volume: 38
                Issue: 4
                Pages: 189-192
                Affiliations
                St. Eriks Eye Hospital, Karolinska Institutet, Stockholm, Sweden
                Article
                Publisher ID: 93069 Other ID: Ophthalmic Res 2006;38:189–192
                DOI: 10.1159/000093069
                PubMed ID: 16679806
                SO-VID: 20cb5c8e-e30e-4185-827f-0752203f5f89
                Copyright © © 2006 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. 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. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 15 June 2005
                Date accepted : 15 December 2005
                Page count
                Tables: 1, References: 27, Pages: 4
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Vision sciences,Ophthalmology & Optometry,Pathology
                Keywords: Growth factor receptors,Retinal detachment,Neovascularization,Pigment-epithelium-derived factor
                Data availability:
                ScienceOpen disciplines: Vision sciences, Ophthalmology & Optometry, Pathology
                Keywords: Growth factor receptors, Retinal detachment, Neovascularization, Pigment-epithelium-derived factor

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