Retinal Degenerative Diseases

Contains the proceedings of the XVI International Symposium on Retinal Degeneration (RD2014), held July 13-18, 2014 at the Asilomar Conference Center in Pacific Grove, California. A majority of those who spoke and presented posters at the meeting contributed to this volume. The Symposium addressed the blinding diseases of inherited retinal degenerations, which have no effective treatments, and age-related macular degeneration, which has no cures, despite the fact that it is an epidemic among the elderly, with 1 in 3-4 affected by the age of 75. The RD2014 Symposium focused on the exciting new developments aimed at understanding these diseases and providing therapies for them.

The volume presents 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; molecular genetics; and developing potential therapeutic measures such as gene therapy and neuroprotective agents for potential pharmaceutical therapy; and several sight restoration approaches, including optogenetics. While advances in these areas of retinal degenerations are included, several new topics either were in their infancy or did not exist at the time of the last RD Symposium, RD2012. These include many new developments in sight restoration using optogenetics, retinal or RPE cell transplantation, stem cell approaches and visual prosthetic devices. In addition, major advances are presented in other basic mechanisms in age-related macular degeneration, several new aspects of gene and antioxidant 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 are reported at the RD2014 meeting and included in this volume.

Inhalt
Part I Age-Related Macular Degeneration (AMD).- Apolipoprotein E Isoforms and AMD.- Role of Chemokines in Shaping Macrophage Activity in AMD.- Biology of p62/sequestosome-1 in Age-Related Macular Degeneration (AMD).- Gene Structure of the 10q26 locus: A Clue to Cracking the ARMS2/HTRA1 Riddle?.- Conditional Induction of Oxidative Stress in RPE: A Mouse Model of Progressive Retinal Degeneration.- Therapeutic Approaches to Histone Reprogramming in Retinal Degeneration.- A Brief Discussion on Lipid Activated Nuclear Receptors and Their Potential Role in Regulating Microglia in Age-Related Macular Degeneration (AMD).- Extracellular Matrix Alterations and Deposit Formation in AMD.- The NLRP3 Inflammasome and its Role in Age-related Macular Degeneration.- Oxidative Stress and the Nrf2 Anti-Oxidant Transcription Factor in Age-Related Macular Degeneration.- Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.- VEGF-A and the NLRP3 Inflammasome in Age-Related Macular Degeneration.- Interrelation Between Oxidative Stress and Complement Activation in Models of Age-Related Macular Degeneration.- Gene-diet Interactions in Age-Related Macular Degeneration.- Challenges in the Development of Therapy for Dry Age-Related Macular Degeneration.- Nanoceria: A Potential Therapeutic for Dry AMD.- -amyloidopathy in the Pathogenesis of Age-Related Macular Degeneration in Correlation with Neurodegenerative Diseases.- Part II Macular Dystrophies/Inherited Macular Degeneration.- Different Mutations in ELOVL4 Affect Very Long Chain Fatty Acid Biosynthesis to Cause Variable Neurological Disorders in Humans.- Mouse Models of Stargardt 3 Dominant Macular Degeneration.- Current Progress in Deciphering Importance of VLC-PUFA in the Retina.- Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy: Similarities to Age-related Macular Degeneration and Potential Therapies.- Part III Inherited Retinal Degenerations.- Hsp90 as a Potential Therapeutic Target in RetinalDisease.- Leber Congenital Amaurosis: Genotypes and Retinal Structure Phenotypes.- A Chemical Mutagenesis Screen Identifies Mouse Models with ERG Defects.- Ablation of Chop Transiently Enhances Photoreceptor Survival But Does Not Prevent Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin.- Identification of a Novel Gene on 10q22 Causing Autosomal Dominant Retinitis Pigmentosa (adRP).- FAM161A and TTC8 Are Differentially Expressed in Non-allelelic Early Onset Retinal Degeneration.- Mutations in the Dynein1 Complex are Permissible for Basal Body Migration in Photoreceptors but Alter Rab6 Localization.- RDS Functional Domains and Dysfunction in Disease.- TULP1 Missense Mutations Induces the Endoplasmic Reticulum Unfolded Protein Response Stress Complex (ER-UPR).- Understanding Cone Photoreceptor Cell Death in Achromatopsia.- Geranylgeranylacetone Suppresses N-methyl-N-nitrosourea-induced Photoreceptor Cell Loss in Mice.- My Retina Tracker™: An On-line International Registry for People Affected with Inherited Orphan Retinal Degenerative Diseases and their Genetic Relatives A New Resource.- A Mini-Review: Animal Models of GUCY2D Leber Congenital Amaurosis (LCA1).- A Comprehensive Review of Mutations in the MERTK Proto-oncogene.- Part IV In Vivo Imaging and Other Diagnostic Advances.- New Developments in Murine Imaging for Assessing Photoreceptor Degeneration In Vivo.- Reliability and repeatability of Cone Density Measurements in Patients with Congenital Achromatopsia.- Quantitative Autofluorescence in Best Vitelliform Macular Dystrophy: RPE Lipofuscin is Not Increased in Non-Lesion Areas of Retina.- Interpretation of Flood-Illuminated Adaptive Optics Images in Subjects with Retinitis Pigmentosa.- Intra-familial Similarity of Wide-Field Fundus Autofluorescence in Inherited
Retinal Dystrophy.- Wide-Field Fundus Autofluorescence for Retinitis Pigmentosa and Cone/Cone-Rod Dystrophy.- The Development of a Cat Model of Retinal Detachment and Re-Attachment.- Part V Mechanisms of Degeneration.- The Role of X-Chromosome Inactivation in Retinal Development and Disease.- A Non-canonical Role for -Secretase in the Retina.- The Consequences of Hypomorphic RPE65 for Rod and Cone Photoreceptors.- The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration.- Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?.- Class I Phosphoinositide 3-Kinase Exerts a Differential Role on Cell Survival and Cell Trafficking in Retina.- Cell Cycle Proteins and Retinal Degeneration: Evidences of New Potential Therapeutic Targets.- Neuronal Nitric Oxide Synthase as a Trigger of the N-methyl-N-nitrosourea-induced Phot...