DIABETIC RETINOPATHY Edited by Mohammad Shamsul Ola Diabetic Retinopathy Edited by Mohammad Shamsul Ola Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Ivana Zec Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published February, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Diabetic Retinopathy, Edited by Mohammad Shamsul Ola p. cm. ISBN 978-953-51-0044-7 Contents Preface IX Part 1 Pathophysiology/Basic Research 1 Chapter 1 Cellular and Molecular Mechanism of Diabetic Retinopathy 3 Mohammad Shamsul Ola and Mohd Imtiaz Nawaz Chapter 2 Gluco-Oxidation of Proteins in Etiology of Diabetic Retinopathy 31 Mohd Wajid Ali Khan, Kamalpreet Banga and Wahid Ali Khan Chapter 3 Diabetic Retinopathy 53 Carlos César Lopes De Jesus Chapter 4 The Molecular Pathogenesis of Diabetic Retinopathy - A Spectrum of Pathology Caused by the Disruption of Inner Blood-Retinal Barrier 67 Byung Joo Lee, and Jeong Hun Kim Chapter 5 Inner Blood-Retinal Barrier Transporters: Relevance to Diabetic Retinopathy 91 Yoshiyuki Kubo and Ken-ichi Hosoya Chapter 6 Fibrovascular Membranes Associated with PDR: Development of Molecular Targets by Global Gene Expression Profiling 109 Shigeo Yoshida, Keijiro Ishikawa, Mitsuru Arima, Ryo Asato, Yukio Sassa and Tatsuro Ishibashi Part 2 Inflammation and Angiogenesis 123 Chapter 7 Inflammation and Diabetic Retinopathy 125 Hongbin Lü VI Contents Chapter 8 Immunological Risk Factors for the Development and Progression of Diabetic Retinopathy 137 Katarzyna Zorena, Dorota Raczyńska, and Krystyna Raczyńska Chapter 9 Inflammation and Angiogenesis in Diabetic Retinopathy 163 Ying Yang, Ying Zhang and Yiping Li Part 3 Clinical Aspects of Diabetic Retinopathy and Retinal Functions 191 Chapter 10 Diabetic Macular Edema 193 Christina Antonopoulos and Manju Subramanian Chapter 11 The Effect of Diabetes Mellitus on Retinal Function 207 Zvia Burgansky-Eliash Chapter 12 Optical Coherence Tomography Findings in Diabetic Macular Edema 225 Desislava Koleva-Georgieva Chapter 13 Preventing Diabetic Retinopathy: Red Lesions Detection in Early Stages 249 C. Mariño, J. Novo, N. Barreira and M.G. Penedo Part 4 Emerging Treatments and Concepts in Diabetic Retinopathy 271 Chapter 14 Treatment of Diabetic Macular Edema – Latest Therapeutic Developments 273 Yeon Sung Moon and Na Rae Kim Chapter 15 Prophylactic Medical Treatment of Diabetic Retinopathy 291 Akihiro Kakehashi, Ayumi Ota, Fumihiko Toyoda, Nozomi Kinoshita, Hiroko Yamagami, Hiroto Obata, Takafumi Matsumoto, Junichi Tsuji, Yoh Dobashi, Wilfred Y. Fujimoto, Masanobu Kawakami and Yasunori Kanazawa Chapter 16 Calcium Dobesilate in Prevention and Treatment of Diabetic Retinopathy 305 Oldřich Farsa Chapter 17 The Role of Sex Hormones in Diabetic Retinopathy 331 Jeffery G. Grigsby, Donald M. Allen, Richard B. Culbert, Gerardo Escobedo, Kalpana Parvathaneni, Brandi S. Betts and Andrew T.C. Tsin Preface During the past few decades great progress has been made in our understanding of pathophysiology, management and treatment of diabetic retinopathy. However, diabetic retinopathy still remains the leading cause of blindness among working adults worldwide. The goal of the book is to provide an update on latest developments in the understanding of pathophysiology of the disease, diagnosis and recent treatments strategies for physicians, ophthalmologists, researchers and medical students. This book covers topics ranging from pathophysiology to clinical aspects of DR and emerging treatments and concepts in diabetic retinopathy. The first section serves as a description of current understanding of the cellular and molecular mechanism of pathophysiology of diabetic retinopathy, in order to develop possible therapeutic strategies. The second section describes general pathogenic concepts of inflammation and angiogenesis. The third section describes clinical aspects and modern diagnostic features. The fourth part discusses recent concepts and emerging treatment strategies relating to the management of diabetic retinopathy. The originality and style of the text by authors have been kept intact, although some aspects overlap in more than one chapter which is justified by their unique approach and interpretation. I am very grateful to all the contributors who have worked very hard to make this book a reality. I would also like to thank staff at INTECH, especially Mr. Igor Babic, Publishing Manager and the technical team who did a great job working together on this book. I hope this book will provide a resource for advancing understanding, as well as improving diagnosis and treatment strategies in the effort to help numerous patients who suffer from DR and are threatened by visual loss. Mohammad Shamsul Ola Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia [...]... of RAS and NF-kB pathway in diabetic induced retinal inflammation by upregulation of ICAM-1, MCP-1 and VEGF which are attenuated by AT-1 receptor blocker [Nagai N, 2007] Therefore, RAS plays an important role in the pathogenesis of diabetic retinopathy and this has led a major interest in RAS inhibitors to prevent retinopathy Cellular and Molecular Mechanism of Diabetic Retinopathy 11 5 Hormones Several... in the retina [Antonetti DA, 2006] ETDR (early treatment of diabetic retinopathy) study demonstrated that elevated serum lipid levels are associated with an increased risk of retinal hard exudates, accompanying 10 Diabetic Retinopathy diabetic macular edema with an increased risk of visual impairment The presence of hard exudates in diabetic retinopathy patients has been shown to be associated with increased...Part 1 Pathophysiology/Basic Research 1 Cellular and Molecular Mechanism of Diabetic Retinopathy Mohammad Shamsul Ola and Mohd Imtiaz Nawaz Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, KSA 1 Introduction Diabetic retinopathy (DR) is one of the most common complications of diabetes affecting millions of working adults worldwide,... involved in the pathogenesis of microvascular disease [Ansquer JC, 2009] High content of lipid in diabetic patients increases the risk of diabetic retinopathy and particularly diabetic macular edema [van Leiden HA, 2002] Still it is unclear how altered lipids level affect the onset and progression of diabetic retinopathy, may be through alterations in metabolic processes that alters concentration of serum... through intracellular reactive oxygen species (ROS) generation, thereby inducing T-cell adhesion to ECs [Yamagishi S, 2007; Inagaki Y, 2003] Fig 1 General features for diabetes induced neurovascular damage in diabetic retinopathy Cellular and Molecular Mechanism of Diabetic Retinopathy 5 AGEs disturb retinal microvascular homeostasis by overproduction of VEGF through the interaction with receptor of... cholesterol lowering drug, statins, may have great potential in the treatment of diabetic retinopathy 4 Renin Angiotensin System (RAS) Hypertension has been identified as a major risk factor of microvascular complications leading to small vessel dysfunction, manifesting the state of diabetic retinopathy In patients with diabetic retinopathy, tight control of blood pressure delays the progression of the disease... from diabetic patients with retinopathy showed high expression of AR protein in nerve fibers, ganglion cells and Müller cells than from nondiabetic individuals [Dagher Z, 2004] Similarly excess accumulation of sorbitol has been found in various tissues including retina of diabetic animals and also in human retinas from nondiabetic eye donors exposed to high glucose similar to the level in nondiabetic... diabetic retinopathy and proliferative vitreoretinopathy Eur Cytokine Netw 2006 Sep;17(3):155-65 [2] Abu El-Asrar AM, Struyf S, Verbeke H, Van Damme J, Geboes K Circulating bonemarrow-derived endothelial precursor cells contribute to neovascularization in diabetic epiretinal membranes Acta Ophthalmol 2011 May;89(3):222-8 [3] Abu El-Asrar AM, Al-Mezaine HS, Ola MS Pathophysiology and management of diabetic. .. Sandirasegarane L, Simpson IA; JDRF Diabetic Retinopathy Center Group Diabetic retinopathy: seeing beyond glucose-induced microvascular disease Diabetes 2006 Sep;55(9):2401-11 [16] Arimura N, Otsuka H, Yamakiri K, Sonoda Y, Nakao S, Noda Y, Hashiguchi T, Maruyama I, Sakamoto T Vitreous mediators after intravitreal bevacizumab or triamcinolone acetonide in eyes with proliferative diabetic retinopathy Ophthalmology... Scicli AG Role of angiotensin II in retinal leukostasis in the diabetic rat Exp Eye Res 2006 Nov;83(5):1041-51 [36] Chibber R, Ben-Mahmud BM, Chibber S, Kohner EM Leukocytes in diabetic retinopathy Curr Diabetes Rev 2007 Feb;3(1):3-14 Cellular and Molecular Mechanism of Diabetic Retinopathy 19 [37] Chung SS, Chung SK Aldose reductase in diabetic microvascular complications Curr Drug Targets 2005 Jun;6(4):475-86 . DIABETIC RETINOPATHY Edited by Mohammad Shamsul Ola Diabetic Retinopathy Edited by Mohammad Shamsul Ola Published by InTech. copies can be obtained from orders@intechweb.org Diabetic Retinopathy, Edited by Mohammad Shamsul Ola p. cm. ISBN 978-953-51-0044-7