Inflammation and Retinal Disease: Complement Biology and Pathology

ISBN-13: 9781441956347 / Angielski / Twarda / 2010 / 170 str.

John D. Lambris; Anthony P. Adamis

Opis

Numerous studies have pointed to the key role of complement in the pathogenesis of retinal disease, particularly age-related macular degeneration (AMD). Reports about new gene associations and links to other physiological pathways are emerging almost on a weekly base. Several promising clinical candidates covering a wide area of potential treatment applications are in the pipelines of both industrial and academic groups. This indicates an increasing interest in complement as a therapeutic target. In view of these exciting discoveries, scientists from around the world convened at the First Aegean Conferences Conference on Inflammation and Retinal Disease: Complement Biology and Pathology (June 10-17, 2007) in Crete, Greece, to discuss recent advances in this rapidly-evolving field. This volume represents a collection of topics on the functions of complement in eye diseases, pathophysiology, protein structures, and complement therapeutics discussed during the conference. Our sincere thanks to the contributing authors for the time and effort they have devoted to writing what I consider exceptionally informative chapters in a book that will have a significant impact on the complement field. We would also like to express my thanks to Rodanthi Lambris for her assistance in collating the chapters and preparing the documents for publication and I gratefully acknowledge the generous help provided by Dimitrios Lambris in managing the organization of this meeting. Finally, I also thank Andrea Macaluso of Springer Publishers for her supervision in this book's production. John D. Lambris Anthony P.

Spis treści

Preface Contributors 1. The Case for Complement and Inflammation in AMD: Open Questions Natalia Karagianni and Anthony P. Adamis Abstract 1. Introduction 2 Drusen 3. Geographic Atrophy 4. Choroidal Neovascularization References 2. The Role of Complement in AMD Peter F. Zipfel, Nadine Lauer and Christine Skerka Abstract 1 Age-related macular degeneration 1.1 The disease 1.2 AMD - a chronic inflammatory disease 2 Age-related macular degeneration – a genetic disorder 3 Effect of the reported SNPs for protein function 3.1 Factor H and other Complement Proteins 3.1.1 Factor H and FHL1 3.1.2 Complement Factor H related proteins (CFHRs) 3.1.3 Other Complement proteins associated with AMD: C2, Factor B and C3 3.2. Gene products of the chromosome 10q26: ARMS-2 and HRTA1 4 Lessons learned from rare disorders (HUS, MPGN) 5 Outlook References 3. Multiple interactions of complement factor H with its ligands in solution: a progress report Stephen J Perkins, Ruodan Nan, Azubuike I. Okemefuna, Keying Li, Sanaullah Khan and Ami Miller Abstract 1. Complement Factor H 2. Structure of Factor H 3. Self-association of Factor H 5. Interaction of Factor H with C-reactive protein 6. Interaction of Factor H with heparin 7. Interaction of Factor H with C3d 8. Conclusions and Future Considerations References 4. Genetic Control of Complement Activation in Humans and Age Related Macular Degeneration Laura A. Hecker, and Albert O. Edwards Abstract 1.Genes associated with AMD 2. Non-genetic factors increasing the risk of AMD 3. Complement proteins and AMD 4. Conclusions References 5. Bisretinoids of RPE Lipofuscin: Trigger for Complement Activation in Age-Related Macular Degeneration Janet R. Sparrow Abstract 1 RPE Lipofuscin and Macular Degeneration 2 Age-related Macular Degeneration and the Complement System 3 Complement Activation by Photoproducts of the RPE Bisretinoid A2E 4 Complement Activation by Oxidized all-trans-retinal-dimer 5 Complement Activation by BisretinoidPhotoproducts is Dependent on Factor B 6 C-Reactive Protein Modulates Complement Activation by RPE Bisretinoids 7 Suppression by POT-3, a C3 Cleavage Inhibitor 8 Summary 9 Acknowledgements References 6. The Role of the Classical Complement Cascade in Synapse Loss during Development and Glaucoma Allison M Rosen and Beth Stevens Abstract 1 Introduction 2 Current Opinion on Glaucoma 3 Animal models of glaucoma 4 Pathological progression of glaucoma 5 Role of Glial Activation in Glaucoma 6 Inflammation and enhanced cytokine production in glaucoma 7 Complement Cascade Upregulation and Activation in Glaucoma 8 Parallels between Complement-mediated Synapse Elimination and Synapses 9 Conclusions and Perspecitves Acknowledgment References: 7. A Role for Complement in Glaucoma? Lizhen Ren, John Danias Abstract 1 Introduction 2 Complement and glaucoma 8. The ATP-binding Cassette Transporter ABCA4: Structural and Functional Properties and Role in Retinal Disease Yaroslav Tsybovsky, Robert S. Molday and Krzysztof Palczewski Abstract 1 Introduction to ABC Transporters 2 Human ABC Transporters 3 ABCA4 and Vision Diseases 4 Molecular View of ABCA4 4.1 Primary Structure 4.2 Localization 4.3 Insights into Topology, Structure and Posttranslational Modifications 4.4 Structural Features of Individual Domains 5 Biological Role of ABCA4 5.1 Identification of Substrate: Biochemical Evidence 5.2 Proposed General Model of Transport 5.3 Abca4 Knockout Mice 5.4 Proposed Role of ABCA4 in the Visual Cycle 5.5 Unresolved Issues 6 ABCA4 Mutations and Autosomal Recessive Macular Degeneration 7 Conclusions References 9. Suppression of Drusen Formation by Compstatin, a Peptide Inhibitor of Complement C3 activation, on Cynomolgus Monkey with Early-Onset Macular Degeneration Zai-Long Chi, Tsunehiko Yoshida, John Lambris, and Takeshi Iwata Abstract 1 AMD and association of complement related genes 2 Activated complement component in drusen 3 Cynomolgus monkey with early-onset macular degene

Blurb

Numerous studies have pointed to the key role of complement in the pathogenesis of retinal disease, particularly age-related macular degeneration (AMD). Reports about new gene associations and links to other physiological pathways are emerging almost on a weekly base. Several promising clinical candidates covering a wide area of potential treatment applications are in the pipelines of both industrial and academic groups. This indicates an increasing interest in complement as a therapeutic target. In view of these exciting discoveries, scientists from around the world convened at the 1st Aegean Conferences Conference on Inflammation and Retinal Disease: Complement Biology and Pathology (June 10-17, 2007) in Crete, Greece, to discuss recent advances in this rapidly-evolving field. This volume represents a collection of topics on the functions of complement in eye diseases, pathophysiology, protein structures, and complement therapeutics discussed during the conference.