Retinal Degenerative Diseases: Mechanisms and Experimental Therapy (Advances in Experimental Medicine and Biology Book 801)

Editors: John D. Ash, Christian Grimm, Joe G. Hollyfield, Robert E. Anderson, Matthew M. LaVail, Catherine Bowes Rickman. — Springer Science+Business Media, LLC 2014. — 841 p. — ISBN 978-1-4614-3208-1. The International Symposia on Retinal Degeneration have been held in conjunction with the biennial International Congress of Eye Research (ICER) since 1984. These RD Symposia have been highly successful and have become one of the most well attended meetings in the field. The RD Symposia are successful because they allow basic and clinician scientists from around the world to convene and present their new research findings in a format that allows sufficient time for discussions and one-on-one interactions in a relaxed atmosphere, where international friendships and collaborations can be fostered. Preface Travel Awards Contributors About the Editors Basic Processes: Development, Physiology and Function Evgenya Y. Popova, Colin J. Barnstable and Samuel Shao-Min Zhang Cell Type-Specific Epigenetic Signatures Accompany Late Stages of Mouse Retina Development Barbara M. Braunger, Cora Demmer and Ernst R. Tamm Programmed Cell Death During Retinal Development of the Mouse Eye Xiaowu Gu, Alaina Reagan, Allen Yen, Faizah Bhatti, Alex W. Cohen and Michael H. Elliott Spatial and Temporal Localization of Caveolin-1 Protein in the Developing Retina Wen-Hsiang Lee, Pratibha Joshi and Rong Wen Glutathione S-Transferase Pi Isoform (GSTP1) Expression in Murine Retina Increases with Developmental Maturity Alexander Aslanidis, Marcus Karlstetter, Yana Walczak, Herbert Jägle and Thomas Langmann RETINA-Specific Expression of Kcnv2 Is Controlled by Cone-Rod Homeobox (Crx) and Neural Retina Leucine Zipper (Nrl) Saravanan Kolandaivelu and Visvanathan Ramamurthy AIPL1 Protein and its Indispensable Role in Cone Photoreceptor Function and Survival Cheryl M. Craft, Jing Huang, Daniel E. Possin and Anita Hendrickson Primate Short-Wavelength Cones Share Molecular Markers with Rods Xi-Qin Ding, Alexander Matveev, Anil Singh, Naoka Komori and Hiroyuki Matsumoto Exploration of Cone Cyclic Nucleotide-Gated Channel-Interacting Proteins Using Affinity Purification and Mass Spectrometry Michael W. Stuck, Shannon M. Conley, Ryan A. Shaw, Roman Wolf and Muna I. Naash Electrophysiological Characterization of Rod and Cone Responses in the Baboon Nonhuman Primate Model Basic Processes: RPE Emeline F. Nandrot Animal Models, in “The Quest to Decipher RPE Phagocytosis” Julian Esteve-Rudd, Vanda S. Lopes, Mei Jiang and David S. Williams In Vivo and in Vitro Monitoring of Phagosome Maturation in Retinal Pigment Epithelium Cells Linda Ruggiero and Silvia C. Finnemann Lack of Effect of Microfilament or Microtubule Cytoskeleton-Disrupting Agents on Restriction of Externalized Phosphatidylserine to Rod Photoreceptor Outer Segment Tips Lisa Shine, Claire Kilty, Jeffrey Gross and Breandan Kennedy Vacuolar ATPases and Their Role in Vision Sonia Guha, Ji Liu, Gabe Baltazar, Alan M. Laties and Claire H. Mitchell Rescue of Compromised Lysosomes Enhances Degradation of Photoreceptor Outer Segments and Reduces Lipofuscin-Like Autofluorescence in Retinal Pigmented Epithelial Cells Olaf Strauß, Claudia Müller, Nadine Reichhart, Ernst R. Tamm and Nestor Mas Gomez The Role of Bestrophin-1 in Intracellular Ca2+ Signaling Basic Processes: Methodology Stephen P. Daiger, Sara J. Bowne, Lori S. Sullivan, Susan H. Blanton, George M. Weinstock, Daniel C. Koboldt, Robert S. Fulton, David Larsen, Peter Humphries, Marian M. Humphries, Eric A. Pierce, Rui Chen and Yumei Li Application of Next-Generation Sequencing to Identify Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa (adRP) Sarwar Zahid, Crandall Peeler, Naheed Khan, Joy Davis, Mahdi Mahmood, John R. Heckenlively and Thiran Jayasundera Digital Quantification of Goldmann Visual Fields (GVFs) as a Means for Genotype–Phenotype Comparisons and Detection of Progression in Retinal Degenerations Shuqian Dong, Yan Liu, Meili Zhu, Xueliang Xu and Yun-Zheng Le Simplified System to Investigate Alteration of Retinal Neurons in Diabetes C. Sippl and E. R. Tamm What Is the Nature of the RGC-5 Cell Line? Genetics in Retinal Disease Karl J. Wahlin, Julien Maruotti and Donald J. Zack Modeling Retinal Dystrophies Using Patient-Derived Induced Pluripotent Stem Cells Byron L. Lam, Stephan L. Züchner, Julia Dallman, Rong Wen, Eduardo C. Alfonso, Jeffery M. Vance and Margaret A. Peričak-Vance Mutation K42E in Dehydrodolichol Diphosphate Synthase (DHDDS) Causes Recessive Retinitis Pigmentosa Daniel F. Schorderet, Maude Bernasconi, Leila Tiab, Tatiana Favez and Pascal Escher IROme, a New High-Throughput Molecular Tool for the Diagnosis of Inherited Retinal Dystrophies—A Price Comparison with Sanger Sequencing Frida Jonsson, Marie S. Burstedt, Ola Sandgren, Anna Norberg and Irina Golovleva Genetic Heterogeneity and Clinical Outcome in a Swedish Family with Retinal Degeneration Caused by Mutations in CRB1 and ABCA4 Genes Frank Zach and Heidi Stöhr FAM161A, a Novel Centrosomal-Ciliary Protein Implicated in Autosomal Recessive Retinitis Pigmentosa AMD: Novel Developments Chi-Chao Chan and Daniel Ardeljan Molecular Pathology of Macrophages and Interleukin-17 in Age-Related Macular Degeneration Michelle Grunin, Shira Hagbi-Levi and Itay Chowers The Role of Monocytes and Macrophages in Age-Related Macular Degeneration Marcus Karlstetter and Thomas Langmann Microglia in the Aging Retina Jin-Dong Ding, Una Kelly, Marybeth Groelle, Joseph G. Christenbury, Wenlan Zhang and Catherine Bowes Rickman The Role of Complement Dysregulation in AMD Mouse Models Bärbel Rohrer, Kannan Kunchithapautham, Andreas Genewsky and Olaf Strauß Prolonged Src Kinase Activation, a Mechanism to Turn Transient, Sublytic Complement Activation into a Sustained Pathological Condition in Retinal Pigment Epithelium Cells Ema Ozaki, Matthew Campbell, Anna-Sophia Kiang, Marian Humphries, Sarah Doyle and Peter Humphries Inflammation in Age-Related Macular Degeneration Zhenzhen Liu, Tingyu Qin, Jilin Zhou, Allen Taylor, Janet R. Sparrow and Fu Shang Impairment of the Ubiquitin-Proteasome Pathway in RPE Alters the Expression of Inflammation Related Genes Chloe M. Stanton and Alan F. Wright Inflammatory Biomarkers for AMD Katayoon B. Ebrahimi, Natalia Fijalkowski, Marisol Cano and James T. Handa Oxidized Low-Density-Lipoprotein-Induced Injury in Retinal Pigment Epithelium Alters Expression of the Membrane Complement Regulatory Factors CD46 and CD59 through Exosomal and Apoptotic Bleb Release Aparna Lakkaraju, Kimberly A. Toops and Jin Xu Should I Stay or Should I Go? Trafficking of Sub-Lytic MAC in the Retinal Pigment Epithelium Toshihide Kurihara, Peter D. Westenskow and Martin Friedlander Hypoxia-Inducible Factor (HIF)/Vascular Endothelial Growth Factor (VEGF) Signaling in the Retina Robert F. Mullins, Aditi Khanna, Desi P. Schoo, Budd A. Tucker, Elliott H. Sohn, Arlene V. Drack and Edwin M. Stone Is Age-Related Macular Degeneration a Microvascular Disease? Felix Grassmann, Iris M. Heid and Bernhard H. F. Weber Genetic Risk Models in Age-Related Macular Degeneration Alex Woodell and Bärbel Rohrer A Mechanistic Review of Cigarette Smoke and Age-Related Macular Degeneration Mark E. Pennesi, Anupam K. Garg, Shu Feng, Keith V. Michaels, Travis B. Smith, Jonathan D. Fay, Alison R. Weiss, Laurie M. Renner, Sawan Hurst, Trevor J. McGill, Anda Cornea, Kay D. Rittenhouse, Marvin Sperling, Joachim Fruebis and Martha Neuringer Measuring Cone Density in a Japanese Macaque (Macaca fuscata) Model of Age-Related Macular Degeneration with Commercially Available Adaptive Optics Goldis Malek Nuclear Receptors as Potential Therapeutic Targets for Age-Related Macular Degeneration Peter D. Westenskow, Toshihide Kurihara and Martin Friedlander Utilizing Stem Cell-Derived RPE Cells as A Therapeutic Intervention for Age-Related Macular Degeneration Müller Cells, Microglia, and Macrophages Minhua Wang and Wai T. Wong Microglia-Müller Cell Interactions in the Retina Sem Genini, William A. Beltran, Veronika M. Stein and Gustavo D. Aguirre Isolation and Ex Vivo Characterization of the Immunophenotype and Function of Microglia/Macrophage Populations in Normal Dog Retina Roswitha Seitz and Ernst R. Tamm Müller Cells and Microglia of the Mouse Eye React Throughout the Entire Retina in Response to the Procedure of an Intravitreal Injection Joseph Fogerty and Joseph C. Besharse Subretinal Infiltration of Monocyte Derived Cells and Complement Misregulation in Mice with AMD-Like Pathology Tembei K. Forkwa, Ernst R. Tamm and Andreas Ohlmann Ambiguous Role of Glucocorticoids on Survival of Retinal Neurons Ana I. Arroba, Noemí Álvarez-Lindo, Nico van Rooijen and Enrique J. de la Rosa Microglia-Müller Glia Crosstalk in the rd10 Mouse Model of Retinitis Pigmentosa Stefanie M. Hauck, Christine von Toerne and Marius Ueffing The Neuroprotective Potential of Retinal Müller Glial Cells Cavit Agca and Christian Grimm Leukemia Inhibitory Factor Signaling in Degenerating Retinas Hong Hao, Janina Gregorski, Haohua Qian, Yichao Li, Chun Y Gao, Sana Idrees and Bin Zhang In Vivo Function of the ER-Golgi Transport Protein LMAN1 in Photoreceptor Homeostasis Suhua Fu, Meili Zhu, John D. Ash, Yunchang Wang and Yun-Zheng Le Investigating the Role of Retinal Müller Cells with Approaches in Genetics and Cell Biology Degenerative Processes: Immune-Related Mechanisms, Genes and Factors Matthew Campbell, Sarah L. Doyle, Ema Ozaki, Paul F. Kenna, Anna-Sophia Kiang, Marian M. Humphries and Peter Humphries An Overview of the Involvement of Interleukin-18 in Degenerative Retinopathies Charles E. Egwuagu Chronic Intraocular Inflammation and Development of Retinal Degenerative Disease Ulrich FO Luhmann, Scott J Robbie, James WB Bainbridge and Robin R Ali The Relevance of Chemokine Signalling in Modulating Inherited and Age-Related Retinal Degenerations Gloriane Schnabolk, Stephen Tomlinson and Bärbel Rohrer The Complement Regulatory Protein CD59: Insights into Attenuation of Choroidal Neovascularization Kazuhiro Ogai, Maki Nishitani, Ayaka Kuwana, Kazuhiro Mawatari, Yoshiki Koriyama, Kayo Sugitani, Hiroshi Nakashima and Satoru Kato Regeneration-Associated Genes on Optic Nerve Regeneration in Fish Retina S. Logan and R. E. Anderson Dominant Stargardt Macular Dystrophy (STGD3) and ELOVL4 Shreyasi Choudhury, Sonali Nashine, Yogesh Bhootada, Mansi Motiwale Kunte, Oleg Gorbatyuk, Alfred S. Lewin and Marina Gorbatyuk Modulation of the Rate of Retinal Degeneration in T17M RHO Mice by Reprogramming the Unfolded Protein Response Ayse Sahaboglu, Sylvia Bolz, Hubert Löwenheim and Francois Paquet-Durand Expression of Poly(ADP-Ribose) Glycohydrolase in Wild-Type and PARG-110 Knock-Out Retina Anh T. H. Nguyen, Matthew Campbell, Anna-Sophia Kiang, Marian M. Humphries and Peter Humphries Current Therapeutic Strategies for P23H RHO-Linked RP Rakesh Kotapati Raghupathy, Daphne L McCulloch, Saeed Akhtar, Turki M Al-Mubrad and Xinhua Shu Pathogenesis of X-linked RP3: Insights from Animal Models Houbin Zhang, Jeanne M. Frederick and Wolfgang Baehr Unc119 Gene Deletion Partially Rescues the GRK1 Transport Defect of Pde6d-/- Cones Cornelia Volz, Myriam Mirza, Thomas Langmann and Herbert Jägle Retinal Function in Aging Homozygous Cln3Δex7/8 Knock-In Mice �� 495 Nora Blanca Caberoy Synergistic Interaction of Tubby and Tubby-Like Protein 1 (Tulp1) Gregory H. Grossman, Craig D. Beight, Lindsey A. Ebke, Gayle J.T. Pauer and Stephanie A. Hagstrom Interaction of Tubby-Like Protein-1 (Tulp1) and Microtubule-Associated Protein (MAP) 1A and MAP1B in the Mouse Retina Theodore G. Drivas and Jean Bennett CEP290 and the Primary Cilium Nasrin Sorusch, Kirsten Wunderlich, Katharina Bauss, Kerstin Nagel-Wolfrum and Uwe Wolfrum Usher Syndrome Protein Network Functions in the Retina and their Relation to Other Retinal Ciliopathies Travis J. Bailey and David R. Hyde The Phenotype of the Good Effort Mutant Zebrafish is Retinal Degeneration by Cell Death and is Linked to the Chromosome Assembly Factor 1b Gene Rong Wen, Julia E. Dallman, Yiwen Li, Stephan L. Züchner, Jeffery M. Vance, Margaret A. Peričak-Vance and Byron L. Lam Knock-Down DHDDS Expression Induces Photoreceptor Degeneration in Zebrafish Michael McClintock, Marc C. Peden and Christine N. Kay Spectral Domain Optical Coherence Tomography Findings in CNGB3-Associated Achromatopsia and Therapeutic Implications Lucia Ziccardi, Camasamudram Vijayasarathy, Ronald A. Bush and Paul A. Sieving Photoreceptor Pathology in the X-Linked Retinoschisis (XLRS) Mouse Results in Delayed Rod Maturation and Impaired Light Driven Transducin Translocation Marijana Samardzija and Christian Grimm Mouse Models for Cone Degeneration F. Paquet-Durand, A. Sahaboglu, J. Dietter, O. Paquet-Durand, B. Hitzmann, M. Ueffing and P. A. R. Ekström How Long Does a Photoreceptor Cell Take to Die? Implications for the Causative Cell Death Mechanisms Degenerative Processes: RPE and Fatty Acids Heike Kroeger, Matthew M. LaVail and Jonathan H. Lin Endoplasmic Reticulum Stress in Vertebrate Mutant Rhodopsin Models of Retinal Degeneration Janet R. Sparrow, Jilin Zhou, Shanti Kaligotla Ghosh and Zhao Liu Bisretinoid Degradation and the Ubiquitin-Proteasome System Analysis of Mouse RPE Sheet Morphology Gives Yi Jiang, X Qi, Micah A. Chrenek, Christopher Gardner, Nupur Dalal, Jeffrey H. Boatright, Hans E. Grossniklaus and John M. Nickerson Discriminatory Categories Min-Lee Chang, Chung-Jung Chiu, Fu Shang and Allen Taylor High Glucose Activates ChREBP-Mediated HIF-1α and VEGF Expression in Human RPE Cells Under Normoxia Annie Y. Chan, Shivani N. Mann, Hui Chen, Donald U. Stone, Daniel J. J. Carr and Nawajes A. Mandal Sphingolipids in Ocular Inflammation Martin-Paul Agbaga, Sreemathi Logan, Richard S. Brush and Robert E. Anderson Biosynthesis of Very Long-Chain Polyunsaturated Fatty Acids in Hepatocytes Expressing ELOVL4 L. D. Marchette, D. M Sherry, R. S Brush, M. Chan, Y. Wen, J. Wang, John D. Ash, R. E. Anderson and N. A. Mandal Very Long Chain Polyunsaturated Fatty Acids and Rod Cell Structure and Function Degenerative Processes: Immune-Related Mechanisms, Genes and Factors Vera L. Bonilha, Mary E. Rayborn, Xiaoping Yang, Chengsong Xie and Huaibin Cai Oxidative Stress Regulation by DJ-1 in the Retinal Pigment Epithelium Kathryn E. Klump and James F. McGinnis The Role of Reactive Oxygen Species in Ocular Malignancy Wei-Chieh Jerry Chiang and Jonathan H. Lin The Effects of IRE1, ATF6, and PERK Signaling on adRPLinked Rhodopsins Jonathan Chou, Stuart Rollins and Amani A Fawzi Role of Endothelial Cell and Pericyte Dysfunction in Diabetic Retinopathy: Review of Techniques in Rodent Models Nathalie Produit-Zengaffinen, Constantin J. Pournaras and Daniel F. Schorderet Autophagy Induction Does Not Protect Retina Against Apoptosis in Ischemia/Reperfusion Model Therapy: Gene Therapy Timothy P. Day, Leah C. Byrne, David V. Schaffer and John G. Flannery Advances in AAV Vector Development for Gene Therapy in the Retina Frank M. Dyka, Sanford L. Boye, Renee C. Ryals, Vince A. Chiodo, Shannon E. Boye and William W. Hauswirth Cone Specific Promoter for Use in Gene Therapy of Retinal Degenerative Diseases Adarsha Koirala, Shannon M Conley and Muna I. Naash Episomal Maintenance of S/MAR-Containing Non-Viral Vectors for RPE-Based Diseases Astra Dinculescu, Seok-Hong Min, Wen-Tao Deng, Qiuhong Li and William W. Hauswirth Gene Therapy in the Rd6 Mouse Model of Retinal Degeneration Zongchao Han, Shannon M. Conley and Muna I. Naash Gene Therapy for Stargardt Disease Associated with ABCA4 Gene Vanda S. Lopes, Tanja Diemer and David S. Williams Assessment of Different Virus-Mediated Approaches for Retinal Gene Therapy of Usher 1B Stylianos Michalakis, Susanne Koch, Vithiyanjali Sothilingam, Marina Garcia Garrido, Naoyuki Tanimoto, Elisabeth Schulze, Elvir Becirovic, Fred Koch, Christina Seide, Susanne C. Beck, Mathias W. Seeliger, Regine Mühlfriedel and Martin Biel Gene Therapy Restores Vision and Delays Degeneration inthe CNGB1−/− Mouse Model of Retinitis Pigmentosa Kerstin Nagel-Wolfrum, Timor Baasov and Uwe Wolfrum Therapy Strategies for Usher Syndrome Type 1C in the Retina Therapy: Protection Yoshiki Koriyama, Marie Kamiya, Kunizo Arai, Kayo Sugitani, Kazuhiro Ogai and Satoru Kato Nipradilol Promotes Axon Regeneration Through S-Nitrosylation of PTEN in Retinal Ganglion Cells Reciprocal Changes in Factor XIII and Retinal Transglutaminase Kayo Sugitani, Kazuhiro Ogai, Yoshiki Koriyama and Satoru Kato Expressions in the Fish Retina During Optic Nerve Regeneration P. Michael Iuvone, Jeffrey H. Boatright, Gianluca Tosini and Keqiang Ye N-Acetylserotonin: Circadian Activation of the BDNF Receptor and Neuroprotection in the Retina and Brain John A. Fuller, Gillian C. Shaw, Delphine Bonnet-Wersinger, Baranda S. Hansen, Cynthia A. Berlinicke, James Inglese and Donald J. Zack A High Content Screening Approach to Identify Molecules Neuroprotective for Photoreceptor Cells Anna-Sophia Kiang, Marian M. Humphries, Matthew Campbell and Peter Humphries Antioxidant Therapy for Retinal Disease Yingbin Fu and Tao Zhang Pathophysilogical Mechanism and Treatment Strategies for Leber Congenital Amaurosis Alison L. Reynolds, David Kent and Breandán N. Kennedy Current and Emerging Therapies for Ocular Neovascularisation Temitope Sasore, Alison L. Reynolds and Breandán N. Kennedy Targeting the PI3K/Akt/mTOR Pathway in Ocular Neovascularization Matthew Rapp, Grace Woo, Muayyad R. Al-Ubaidi, S. Patricia Becerra and Preeti Subramanian Pigment Epithelium-Derived Factor Protects Cone Photoreceptor-Derived 661W Cells from Light Damage Through Akt Activation Lily L. Wong and James F. McGinnis Nanoceria as Bona Fide Catalytic Antioxidants in Medicine: What We Know and What We Want to Know... Xue Cai, Junji Yodoi, Sudipta Seal and James F. McGinnis Nanoceria and Thioredoxin Regulate a Common Antioxidative Gene Network in tubby Mice Toshiaki Abe, Yumi Tokita-Ishikawa, Hideyuki Onami, Yuki Katsukura, Hirokazu Kaji, Matsuhiko Nishizawa and Nobuhiro Nagai Intrascleral Transplantation of a Collagen Sheet with Cultured Brain-Derived Neurotrophic Factor Expressing Cells Partially Rescues the Retina from Damage due to Acute High Intraocular Pressure Machelle T. Pardue, Vincent T. Ciavatta and John R. Hetling Neuroprotective Effects of Low Level Electrical Stimulation Therapy on Retinal Degeneration Index This book will contain the proceedings of the XV International Symposium on Retinal Degeneration (RD2012). A majority of those who will speak and present posters at the meeting will contribute to this volume. The blinding diseases of inherited retinal degenerations have no treatments, and age-related macular degeneration has no cures, despite the fact that it is an epidemic among the elderly, with 1 in 3-4 affected by the age of 70. The RD Symposium will focus on the exciting new developments aimed at understanding these diseases and providing therapies for them. Since most major scientists in the field of retinal degenerations attend the biennial RD Symposia, they are known by most as the “best” and “most important” meetings in the field. The volume will present representative state-of-the-art research in almost all areas of retinal degenerations, ranging from cytopathologic, physiologic, diagnostic and clinical aspects; animal models; mechanisms of cell death; candidate genes, cloning, mapping and other aspects of molecular genetics; and developing potential therapeutic measures such as gene therapy and neuroprotective agents for potential pharmaceutical therapy. While advances in these areas of retinal degenerations will be described, there will be many new topics that either were in their infancy or did not exist at the time of the last RD Symposium, RD2010. These include the role of inflammation and immunity, as well as other basic mechanisms, in age-related macular degeneration, several new aspects of gene therapy, and revolutionary new imaging and functional testing that will have a huge impact on the diagnosis and following the course of retinal degenerations, as well as to provide new quantitative endpoints for clinical trials. The retina is an approachable part of the central nervous system (CNS), and there is a major interest in neuroprotective and gene therapy for CNS diseases and neurodegenerations, in general. It should be noted that with successful and exciting initial clinical trials in neuroprotective and gene therapy, including the restoration of sight in blind children, the retinal degeneration therapies are leading the way towards new therapeutic measures for neurodegenerations of the CNS. Many of the successes recently reported in these areas of retinal degeneration sprang from collaborations established at previous RD Symposia, and many of those will be reported at the RD2010 meeting and included in the proposed volume. We anticipate the excitement of those working in the field and those afflicted with retinal degenerations will be reflected in the volume.