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      Macular Capillary Blood Flow in Patients with Diffuse Diabetic Macular Edema without Vitreomacular Traction

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          Abstract

          Background: To evaluate macular microcirculation in patients with unilateral diffuse diabetic macular edema (DME) in order to determine whether the alteration in macular microcirculation is associated with development of diffuse DME without vitreomacular traction. Methods: According to the presence of epiretinal membrane (ERM), 27 patients having unilateral diffuse DME were divided into DME without ERM (non-ERM-DME group, n = 12) and with ERM (ERM-DME group, n = 15). Twelve patients with macular edema associated with unilateral branch vein obstruction (BVO) and 10 nondiabetic healthy subjects were enrolled as controls. Macular blood flow measured by Heidelberg retinal flowmeter was compared between the edematous eye and the nonedematous fellow eye of each patient and between groups. The macular thickness was evaluated with optical coherence tomography. Results: The mean macular blood flow was significantly higher than that of the contralateral eyes in edematous eyes of non-ERM-DME group (798.8 vs. 379.8 AU, p < 0.001). By contrast, in the ERM-DME group, the mean macular blood flow of DME eyes was similar to that of fellow eyes (575.9 vs. 596.4 AU, p = 0.538). The macular capillary blood flow in patients with BVO was not significantly different compared with nondiabetic controls (p = 0.967). Conclusions: The results suggest that the alteration of macular microcirculation may play a role in the pathogenesis of diffuse DME without vitreomacular traction.

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          Most cited references 30

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          Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells.

          Vascular endothelial growth factor (VEGF) is a regulator of vasculogenesis and angiogenesis. To investigate the role of nitric oxide (NO) in VEGF-induced proliferation and in vitro angiogenesis, human umbilical vein endothelial cells (HUVEC) were used. VEGF stimulated the growth of HUVEC in an NO-dependent manner. In addition, VEGF promoted the NO-dependent formation of network-like structures in HUVEC cultured in three dimensional (3D) collagen gels. Exposure of cells to VEGF led to a concentration-dependent increase in cGMP levels, an indicator of NO production, that was inhibited by nitro-L-arginine methyl ester. VEGF-stimulated NO production required activation of tyrosine kinases and increases in intracellular calcium, since tyrosine kinase inhibitors and calcium chelators attenuated VEGF-induced NO release. Moreover, two chemically distinct phosphoinositide 3 kinase (PI-3K) inhibitors attenuated NO release after VEGF stimulation. In addition, HUVEC incubated with VEGF for 24 h showed an increase in the amount of endothelial NO synthase (eNOS) protein and the release of NO. In summary, both short- and long-term exposure of human EC to VEGF stimulates the release of biologically active NO. While long-term exposure increases eNOS protein levels, short-term stimulation with VEGF promotes NO release through mechanisms involving tyrosine and PI-3K kinases, suggesting that NO mediates aspects of VEGF signaling required for EC proliferation and organization in vitro.
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            Erythropoietin and VEGF exhibit equal angiogenic potential.

            Erythropoietin (Epo) is a hormone regulating proliferation and differentiation of erythroid cells. The hypothesis that hematopoietic and endothelial cells share a common hemangioblast progenitor among others is based on the finding that both cell lineages express cell surface antigens like CD31 and CD34. In this study we investigated the angiogenic potential of recombinant human erythropoietin (rHuEpo) on endothelial cells derived from human adult myocardial tissue. In addition, we compared the angiogenic potential of rHuEpo to that of other cytokines (VEGF, aFGF) and combinations of growth factors. Samples of myocardial tissue (cardiac auricle) were obtained during coronary bypass surgery, embedded in a fibrin gel matrix, and cultured for 21 days. Capillary sprouting was measured with an eye-piece graticule under an inverted-phase contrast microscope. Tube-forming endothelial cells were characterized by immunohistochemistry and RT-PCR. Using a concentration of 2.5 U/ml, we found that rHuEpo stimulates capillary outgrowth up to 220%, compared to the nonstimulated physiological outgrowth. Epo therefore exhibits the same angiogenic potential on endothelial cells in our in vitro assay as VEGF(165) (230% increase). Erythropoietin stimulates capillary outgrowth in an in vitro angiogenesis assay using adult human myocardial tissue. This implies a role of erythropoietin in vasoproliferative processes. rHuEpo may serve as a direct angiogenic substance in patients with ischemic heart disease.
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              The pathogenesis of diabetic retinopathy: old concepts and new questions

               J. Cai,  M. Boulton (2002)
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                Author and article information

                Journal
                ORE
                Ophthalmic Res
                10.1159/issn.0030-3747
                Ophthalmic Research
                S. Karger AG
                0030-3747
                1423-0259
                2009
                September 2009
                27 May 2009
                : 42
                : 2
                : 73-80
                Affiliations
                aDepartment of Ophthalmology, College of Medicine and bResearch Institute for Sensory Organs, Medical Research Center, Seoul National University, Seoul, Korea
                Article
                220599 Ophthalmic Res 2009;42:73–80
                10.1159/000220599
                19478545
                © 2009 S. Karger AG, Basel

                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.

                Page count
                Figures: 4, Tables: 2, References: 42, Pages: 8
                Categories
                Original Paper

                Vision sciences, Ophthalmology & Optometry, Pathology

                Diabetic retinopathy, Blood flow, Macular edema

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