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      Decreased Ratio of VEGF165b/VEGF in Aqueous Humor Predicts Progression of Diabetic Retinopathy

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          Abstract

          Background: Different splicing of vascular endothelial growth factor (VEGF) gene results in 2 families of VEGF, the proangiogenic isoforms (VEGF<sub>xxx</sub>a) and the antiangiogenic isoforms (VEGF<sub>xxx</sub>b). VEGF<sub>165</sub>b is the major antiangiogenic isoform of VEGF and the most studied member of the VEGF<sub>xxx</sub>b family so far. Objectives: To determine the concentration of VEGF<sub>165</sub>b and VEGF in the aqueous humor (AH) in diabetic eyes with or without diabetic retinopathy (DR) and to address the predictive value of VEGF<sub>165</sub>b/VEGF ratio for progression of DR. Methods: AH samples from 20 eyes in healthy controls (CON group), 40 eyes in diabetic patients without DR (nDR group), and 30 eyes in diabetic patients with mild nonproliferative DR (DR group) were collected. All of the patients were followed up for at least 5 years. VEGF<sub>165</sub>b and VEGF levels of AH samples were measured by enzyme-linked immunosorbent assay (ELISA). The predictive value of the initial VEGF<sub>165</sub>b/VEGF ratio for progression of DR was studied. Results: The mean concentration of VEGF<sub>165</sub>b significantly decreased in diabetic eyes vs. controls. The mean concentration of VEGF significantly increased in the DR group vs. the CON group. The VEGF<sub>165</sub>b/VEGF ratio was significantly lower in diabetic patients compared to the CON group. The VEGF<sub>165</sub>b/VEGF ratio was significantly lower in diabetic patients compared to the control group. The mean follow-up was 66.1months (range 60–71 months). The risk of DR progression was greater with a lower VEGF<sub>165</sub>b/VEGF ratio. Conclusion: The VEGF<sub>165</sub>b/VEGF ratio is lower in the AH of DR patients and the decreased ratio of VEGF<sub>165</sub>b/VEGF predicts DR progression.

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          Global Prevalence and Major Risk Factors of Diabetic Retinopathy

          OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A1c, and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.
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            Diagnosis and Classification of Diabetes Mellitus

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              VEGF-A splicing: the key to anti-angiogenic therapeutics?

               S. Harper,  D Bates (2008)
              The physiology of microvessels limits the growth and development of tumours. Tumours gain nutrients and excrete waste through growth-associated microvessels. New anticancer therapies target this microvasculature by inhibiting vascular endothelial growth factor A (VEGF-A) splice isoforms that promote microvessel growth. However, certain VEGF-A splice isoforms in normal tissues inhibit growth of microvessels. Thus, it is the VEGF-A isoform balance, which is controlled by mRNA splicing, that orchestrates angiogenesis. Here, we highlight the functional differences between the pro-angiogenic and the anti-angiogenic VEGF-A isoform families and the potential to harness the synthetic capacity of cancer cells to produce factors that inhibit, rather than aid, cancer growth.
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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
                2020
                December 2020
                28 April 2020
                : 63
                : 6
                : 517-523
                Affiliations
                aDepartment of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China
                bDepartment of Ophthalmology, Shanxi Eye Hospital, Taiyuan City, China
                cDepartment of Ophthalmology, Shenyang Aier Eye Hospital, Shenyang City, China
                dDepartment of Ophthalmology, Emory University, Atlanta, Georgia, USA
                Author notes
                *Song Chen and Tiangeng He, Tianjin Medical University General Hospital, Department of Ophthalmology, Anshan Rd. 154, Tianjin, Tianjin 300052 (China), chensongzyy@163.com and hetiangeng@126.com
                Article
                508250 Ophthalmic Res 2020;63:517–523
                10.1159/000508250
                32344407
                © 2020 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: 3, Tables: 2, Pages: 7
                Categories
                Retina

                Vision sciences, Ophthalmology & Optometry, Pathology

                Diabetic retinopathy, Progression, VEGF165b, VEGF

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