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

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. Front Matter....Pages i-lxi Front Matter....Pages 1-1 Cell Type-Specific Epigenetic Signatures Accompany Late Stages of Mouse Retina Development....Pages 3-8 Programmed Cell Death During Retinal Development of the Mouse Eye....Pages 9-13 Spatial and Temporal Localization of Caveolin-1 Protein in the Developing Retina....Pages 15-21 Glutathione S-Transferase Pi Isoform (GSTP1) Expression in Murine Retina Increases with Developmental Maturity....Pages 23-30 RETINA-Specific Expression of Kcnv2 Is Controlled by Cone-Rod Homeobox (Crx) and Neural Retina Leucine Zipper (Nrl)....Pages 31-41 AIPL1 Protein and its Indispensable Role in Cone Photoreceptor Function and Survival....Pages 43-48 Primate Short-Wavelength Cones Share Molecular Markers with Rods....Pages 49-56 Exploration of Cone Cyclic Nucleotide-Gated Channel-Interacting Proteins Using Affinity Purification and Mass Spectrometry....Pages 57-65 Electrophysiological Characterization of Rod and Cone Responses in the Baboon Nonhuman Primate Model....Pages 67-73 Front Matter....Pages 75-75 Animal Models, in “ The Quest to Decipher RPE Phagocytosis ”....Pages 77-83 In Vivo and in Vitro Monitoring of Phagosome Maturation in Retinal Pigment Epithelium Cells....Pages 85-90 Lack of Effect of Microfilament or Microtubule Cytoskeleton-Disrupting Agents on Restriction of Externalized Phosphatidylserine to Rod Photoreceptor Outer Segment Tips....Pages 91-96 Vacuolar ATPases and Their Role in Vision....Pages 97-103 Rescue of Compromised Lysosomes Enhances Degradation of Photoreceptor Outer Segments and Reduces Lipofuscin-Like Autofluorescence in Retinal Pigmented Epithelial Cells....Pages 105-111 The Role of Bestrophin-1 in Intracellular Ca 2+ Signaling....Pages 113-119 Front Matter....Pages 121-121 Application of Next-Generation Sequencing to Identify Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa (adRP)....Pages 123-129 Digital Quantification of Goldmann Visual Fields (GVFs) as a Means for Genotype–Phenotype Comparisons and Detection of Progression in Retinal Degenerations....Pages 131-137 Simplified System to Investigate Alteration of Retinal Neurons in Diabetes....Pages 139-143 What is the Nature of the RGC-5 Cell Line?....Pages 145-154 Front Matter....Pages 155-155 Modeling Retinal Dystrophies Using Patient-Derived Induced Pluripotent Stem Cells....Pages 157-164 Front Matter....Pages 155-155 Mutation K42E in Dehydrodolichol Diphosphate Synthase (DHDDS) Causes Recessive Retinitis Pigmentosa....Pages 165-170 IROme, a New High-Throughput Molecular Tool for the Diagnosis of Inherited Retinal Dystrophies—A Price Comparison with Sanger Sequencing....Pages 171-176 Genetic Heterogeneity and Clinical Outcome in a Swedish Family with Retinal Degeneration Caused by Mutations in CRB1 and ABCA4 Genes....Pages 177-183 FAM161A, a Novel Centrosomal-Ciliary Protein Implicated in Autosomal Recessive Retinitis Pigmentosa....Pages 185-190 Front Matter....Pages 191-191 Molecular Pathology of Macrophages and Interleukin-17 in Age-Related Macular Degeneration....Pages 193-198 The Role of Monocytes and Macrophages in Age-Related Macular Degeneration....Pages 199-205 Microglia in the Aging Retina....Pages 207-212 The Role of Complement Dysregulation in AMD Mouse Models....Pages 213-219 Prolonged Src Kinase Activation, a Mechanism to Turn Transient, Sublytic Complement Activation into a Sustained Pathological Condition in Retinal Pigment Epithelium Cells....Pages 221-227 Inflammation in Age-Related Macular Degeneration....Pages 229-235 Impairment of the Ubiquitin-Proteasome Pathway in RPE Alters the Expression of Inflammation Related Genes....Pages 237-250 Inflammatory Biomarkers for AMD....Pages 251-257 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....Pages 259-265 Should I Stay or Should I Go? Trafficking of Sub-Lytic MAC in the Retinal Pigment Epithelium....Pages 267-274 Hypoxia-Inducible Factor (HIF)/Vascular Endothelial Growth Factor (VEGF) Signaling in the Retina....Pages 275-281 Is Age-Related Macular Degeneration a Microvascular Disease?....Pages 283-289 Genetic Risk Models in Age-Related Macular Degeneration....Pages 291-300 A Mechanistic Review of Cigarette Smoke and Age-Related Macular Degeneration....Pages 301-307 Measuring Cone Density in a Japanese Macaque ( Macaca fuscata ) Model of Age-Related Macular Degeneration with Commercially Available Adaptive Optics....Pages 309-316 Nuclear Receptors as Potential Therapeutic Targets for Age-Related Macular Degeneration....Pages 317-321 Front Matter....Pages 191-191 Utilizing Stem Cell-Derived RPE Cells as A Therapeutic Intervention for Age-Related Macular Degeneration....Pages 323-329 Front Matter....Pages 331-331 Microglia-Müller Cell Interactions in the Retina....Pages 333-338 Isolation and Ex Vivo Characterization of the Immunophenotype and Function of Microglia/Macrophage Populations in Normal Dog Retina....Pages 339-345 Müller Cells and Microglia of the Mouse Eye React Throughout the Entire Retina in Response to the Procedure of an Intravitreal Injection....Pages 347-353 Subretinal Infiltration of Monocyte Derived Cells and Complement Misregulation in Mice with AMD-Like Pathology....Pages 355-363 Ambiguous Role of Glucocorticoids on Survival of Retinal Neurons....Pages 365-371 Microglia-Müller Glia Crosstalk in the rd10 Mouse Model of Retinitis Pigmentosa....Pages 373-379 The Neuroprotective Potential of Retinal Müller Glial Cells....Pages 381-387 Leukemia Inhibitory Factor Signaling in Degenerating Retinas....Pages 389-394 In Vivo Function of the ER-Golgi Transport Protein LMAN1 in Photoreceptor Homeostasis....Pages 395-399 Investigating the Role of Retinal Müller Cells with Approaches in Genetics and Cell Biology....Pages 401-405 Front Matter....Pages 407-407 An Overview of the Involvement of Interleukin-18 in Degenerative Retinopathies....Pages 409-415 Chronic Intraocular Inflammation and Development of Retinal Degenerative Disease....Pages 417-425 The Relevance of Chemokine Signalling in Modulating Inherited and Age-Related Retinal Degenerations....Pages 427-433 The Complement Regulatory Protein CD59: Insights into Attenuation of Choroidal Neovascularization....Pages 435-440 Regeneration-Associated Genes on Optic Nerve Regeneration in Fish Retina....Pages 441-446 Dominant Stargardt Macular Dystrophy (STGD3) and ELOVL4....Pages 447-453 Modulation of the Rate of Retinal Degeneration in T17M RHO Mice by Reprogramming the Unfolded Protein Response.....Pages 455-462 Expression of Poly(ADP-Ribose) Glycohydrolase in Wild-Type and PARG-110 Knock-Out Retina....Pages 463-469 Current Therapeutic Strategies for P23H RHO-Linked RP....Pages 471-476 Front Matter....Pages 407-407 Pathogenesis of X-linked RP3: Insights from Animal Models....Pages 477-485 Retinal Function in Aging Homozygous Cln3 Δex7/8 Knock-In Mice....Pages 487-493 Synergistic Interaction of Tubby and Tubby-Like Protein 1 (Tulp1)....Pages 495-501 Interaction of Tubby-Like Protein-1 (Tulp1) and Microtubule-Associated Protein (MAP) 1A and MAP1B in the Mouse Retina....Pages 503-509 CEP290 and the Primary Cilium....Pages 511-518 Usher Syndrome Protein Network Functions in the Retina and their Relation to Other Retinal Ciliopathies....Pages 519-525 The Phenotype of the Good Effort Mutant Zebrafish is Retinal Degeneration by Cell Death and is Linked to the Chromosome Assembly Factor 1b Gene....Pages 527-533 Knock-Down DHDDS Expression Induces Photoreceptor Degeneration in Zebrafish....Pages 535-541 Spectral Domain Optical Coherence Tomography Findings in CNGB3-Associated Achromatopsia and Therapeutic Implications....Pages 543-550 Photoreceptor Pathology in the X-Linked Retinoschisis (XLRS) Mouse Results in Delayed Rod Maturation and Impaired Light Driven Transducin Translocation....Pages 551-557 Mouse Models for Cone Degeneration....Pages 559-566 How Long Does a Photoreceptor Cell Take to Die? Implications for the Causative Cell Death Mechanisms....Pages 567-573 Front Matter....Pages 575-581 Endoplasmic Reticulum Stress in Vertebrate Mutant Rhodopsin Models of Retinal Degeneration....Pages 583-583 Bisretinoid Degradation and the Ubiquitin-Proteasome System....Pages 585-592 Analysis of Mouse RPE Sheet Morphology Gives Discriminatory Categories....Pages 593-600 High Glucose Activates ChREBP-Mediated HIF-1α and VEGF Expression in Human RPE Cells Under Normoxia....Pages 601-607 Sphingolipids in Ocular Inflammation....Pages 609-621 Biosynthesis of Very Long-Chain Polyunsaturated Fatty Acids in Hepatocytes Expressing ELOVL4....Pages 623-629 Very Long Chain Polyunsaturated Fatty Acids and Rod Cell Structure and Function....Pages 631-636 Front Matter....Pages 637-645 Oxidative Stress Regulation by DJ-1 in the Retinal Pigment Epithelium....Pages 647-647 The Role of Reactive Oxygen Species in Ocular Malignancy....Pages 649-654 The Effects of IRE1, ATF6, and PERK Signaling on adRP-Linked Rhodopsins....Pages 655-659 Role of Endothelial Cell and Pericyte Dysfunction in Diabetic Retinopathy: Review of Techniques in Rodent Models....Pages 661-667 Autophagy Induction Does Not Protect Retina Against Apoptosis in Ischemia/Reperfusion Model....Pages 669-675 Front Matter....Pages 677-683 Advances in AAV Vector Development for Gene Therapy in the Retina....Pages 685-685 Cone Specific Promoter for Use in Gene Therapy of Retinal Degenerative Diseases....Pages 687-693 Episomal Maintenance of S/MAR-Containing Non-Viral Vectors for RPE-Based Diseases....Pages 695-701 Gene Therapy in the Rd6 Mouse Model of Retinal Degeneration....Pages 703-709 Gene Therapy for Stargardt Disease Associated with ABCA4 Gene....Pages 711-718 Assessment of Different Virus-Mediated Approaches for Retinal Gene Therapy of Usher 1B....Pages 719-724 Gene Therapy Restores Vision and Delays Degeneration in the CNGB1 −/− Mouse Model of Retinitis Pigmentosa....Pages 725-731 Therapy Strategies for Usher Syndrome Type 1C in the Retina....Pages 733-739 Front Matter....Pages 741-747 Nipradilol Promotes Axon Regeneration Through S-Nitrosylation of PTEN in Retinal Ganglion Cells....Pages 749-749 Reciprocal Changes in Factor XIII and Retinal Transglutaminase Expressions in the Fish Retina During Optic Nerve Regeneration....Pages 751-757 N -Acetylserotonin: Circadian Activation of the BDNF Receptor and Neuroprotection in the Retina and Brain....Pages 759-764 A High Content Screening Approach to Identify Molecules Neuroprotective for Photoreceptor Cells....Pages 765-771 Antioxidant Therapy for Retinal Disease....Pages 773-781 Pathophysilogical Mechanism and Treatment Strategies for Leber Congenital Amaurosis....Pages 783-789 Current and Emerging Therapies for Ocular Neovascularisation....Pages 791-796 Front Matter....Pages 797-804 Targeting the PI3K/Akt/mTOR Pathway in Ocular Neovascularization....Pages 749-749 Pigment Epithelium-Derived Factor Protects Cone Photoreceptor-Derived 661W Cells from Light Damage Through Akt Activation....Pages 805-811 Nanoceria as Bona Fide Catalytic Antioxidants in Medicine: What We Know and What We Want to Know.......Pages 813-820 Nanoceria and Thioredoxin Regulate a Common Antioxidative Gene Network in tubby Mice....Pages 821-828 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....Pages 829-836 Neuroprotective Effects of Low Level Electrical Stimulation Therapy on Retinal Degeneration....Pages 837-843 Back Matter....Pages 845-851 ....Pages 853-862