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E-grāmata: Retinal Degenerative Diseases: Mechanisms and Experimental Therapy

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This book contains the proceedings of the XVIII International Symposium on Retinal Degeneration (RD2018). A majority of those who spoke  and presented posters at the meeting contributed 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 focused 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 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; 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 were described, there will be many new topics that either are in their infancy or did not exist at the time of the last RD Symposium, RD2016. 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 were reported at the RD2016 meeting and included in the current volume. We anticipate the excitement of those working in the field and those afflicted with retinal degenerations is reflected in the volume.





 
Part I Age-Related Macular Degeneration (AMD)
1 AMD-Associated HTRA1 Variants Do Not Influence TGF-β Signaling in Microglia
3(6)
Isha Akhtar-Schaefer
Raphael Reuten
Manuel Koch
Markus Pietsch
Thomas Langmann
2 A Review of Pathogenic Drivers of Age-Related Macular Degeneration, Beyond Complement, with a Focus on Potential Endpoints for Testing Therapeutic Interventions in Preclinical Studies
9(6)
Mayur Choudhary
Goldis Malek
3 GPR143 Signaling and Retinal Degeneration
15(6)
Anna G. Figueroa
Brian S. McKay
4 Isolation of Retinal Exosome Biomarkers from Blood by Targeted Immunocapture
21(6)
Mikael Klingeborn
Nikolai P. Skiba
W. Daniel Stamer
Catherine Bowes Rickman
5 Systemic Inflammatory Disease and AMD Comorbidity
27(6)
Gloriane Schnabolk
6 Adaptive and Maladaptive Complement Activation in the Retina
33(6)
Sean M. Silverman
Wai T. Wong
7 Long-Chain Polyunsaturated Fatty Acids and Age-Related Macular Degeneration
39(6)
Dorota Skowronska-Krawczyk
Daniel L. Chao
8 Melatonin as the Possible Link Between Age-Related Retinal Regeneration and the Disrupted Circadian Rhythm in Elderly
45(6)
Nadezda A. Stepicheva
Joseph Weiss
Peng Shang
Meysam Yazdankhah
Sayan Ghosh
Imran A. Bhutto
Stacey Hose
J. Samuel Zigler Jr
Debasish Sinha
9 Active Cholesterol Efflux in the Retina and Retinal Pigment Epithelium
51(6)
Federica Storti
Christian Grimm
10 Systematic Injection of Low-Dose LPS Transiently Improves the Retina Function and Structure of a Mouse Model of Geographic Atrophy
57(8)
Brianna M. Young
Cristhian J. Ildefonso
Part II Gene Therapies
11 Small Molecule-Based Inducible Gene Therapies for Retinal Degeneration
65(6)
Shyamtanu Datta
Hui Peng
John D. Hulleman
12 RNA-Based Therapeutic Strategies for Inherited Retinal Dystrophies
71(8)
Alejandro Garanto
13 A Comparison of Inducible Gene Expression Platforms: Implications for Recombinant Adeno-Associated Virus (rAAV) Vector-Mediated Ocular Gene Therapy
79(6)
Daniel M. Lipinski
14 Emerging Concepts for RNA Therapeutics for Inherited Retinal Disease
85(6)
Spencer M. Moore
Dorota Skowronska-Krawczyk
Daniel L. Chao
15 In Vivo Assessment of Potential Therapeutic Approaches for USH2A-Associated Diseases
91(6)
Nachiket D. Pendse
Veronica Lamas
Basil S. Pawlyk
Morgan L. Maeder
Zheng-Yi Chen
Eric A. Pierce
Qin Liu
16 Gene and Cell Therapy for AIPLl-Associated Leber Congenital Amaurosis: Challenges and Prospects
97(6)
Pedro R. L. Perdigao
Jacqueline van der Spuy
17 Advancing Gene Therapy for PDE6A Retinitis Pigmentosa
103(6)
Simon M. Petersen-Jones
Laurence M. Occelli
Martin Biel
Stylianos Michalakis
18 Systemic Delivery of Genes to Retina Using Adeno-Associated Viruses
109(4)
Chiab P. Simpson
Susan N. Bolch
Ping Zhu
Frances Weidert
Astra Dinculescu
Ekaterina S. Lobanova
19 Progress in Gene Therapy for Rhodopsin Autosomal Dominant Retinitis Pigmentosa
113(6)
Raghavi Sudharsan
William A. Beltran
20 A Discovery with Potential to Revitalize Hammerhead Ribozyme Therapeutics for Treatment of Inherited Retinal Degenerations
119(6)
Alexandria J. Trujillo
Jason M. Myers
Zahra S. Fayazi
Mark C. Butler
Jack M. Sullivan
21 Temporal Distribution Patterns of Alexa Fluor 647-Conjugated CeNPs in the Mouse Retina After a Single Intravitreal Injection
125(8)
Lily L. Wong
Swetha Barkam
Sudipta Seal
James F. McGinnis
Part III In-Vivo Imaging for Structure and Function
22 Dysflective Cones
133(6)
Jacque L. Duncan
Austin Roorda
23 Multimodal Imaging in Choroideremia
139(6)
Katharina G. Foote
Austin Roorda
Jacque L. Duncan
24 Functional Assessment of Vision Restoration
145(6)
Juliette E. McGregor
David R. Williams
William H. Merigan
25 Noninvasive Diagnosis of Regional Alteration of Retinal Morphology and Structure with Optical Coherence Tomography in Rodents
151(8)
Fangfang Qiu
Meili Zhu
Yun-Zheng Le
Part IV Immunity and Inflammation
26 Microglial Cell Dysfunction in CRB1-Associated Retinopathies
159(6)
C. Henrique Alves
Jan Wijnholds
27 Innate Immune Response Following AAV Administration
165(4)
D. L. Dauletbekov
J. K. Pfromm
A. K. Fritz
M. D. Fischer
28 The Role of Caveolin-1 in Retinal Inflammation
169(6)
Jami M. Gurley
Michael H. Elliott
29 Increased Protein Citrullination as a Trigger for Resident Immune System Activation, Intraretinal Inflammation, and Promotion of Anti-retinal Autoimmunity: Intersecting Paths in Retinal Degenerations of Potential Therapeutic Relevance
175(6)
Alessandro Iannaccone
Marko Z. Radic
30 Identification of a Unique Subretinal Microglia Type in Retinal Degeneration Using Single Cell RNA-Seq
181(8)
Chen Yu
Daniel R. Saban
Part V Inherited Retinal Degenerations
31 Description of Two Siblings with Apparently Severe CEP290 Mutations and Unusually Mild Retinal Disease Unrelated to Basal Exon Skipping or Nonsense-Associated Altered Splicing
189(8)
Iris Barny
Isabelle Perrault
Marlene Rio
Helene Dollfus
Sabine Defoort-Dhellemmes
Josseline Kaplan
Jean-Michel Rozet
Xavier Gerard
32 Detection of Large Structural Variants Causing Inherited Retinal Diseases
197(6)
Stephen P. Daiger
Lori S. Sullivan
Sara J. Bowne
Elizabeth D. Cadena
Dan Koboldt
Kinga M. Bujakowska
Eric A. Pierce
33 A Novel FLVCR1 Variant Implicated in Retinitis Pigmentosa
203(6)
Adrian Dockery
Matthew Carrigan
Niamh Wynne
Kirk Stephenson
David Keegan
Paul F. Kenna
G. Jane Farrar
34 Natural History and Genotype-Phenotype Correlations in RDH12- Associated Retinal Degeneration
209(6)
Abigail T. Fahim
Debra A. Thompson
35 Scaling New Heights in the Genetic Diagnosis of Inherited Retinal Dystrophies
215(6)
Roser Gonzalez-Duarte
Marta de Castro-Miro
Miquel Tuson
Valeria Ramirez-Castaneda
Rebeca Valero Gils
Gemma Marfany
36 Mutations in VSX2, SOX2, and FOXE3 Identified in Patients with Micro-/Anophthalmia
221(6)
Imen Habibi
Mohamed Youssef
Eman Marzouk
Nihal El Shakankiri
Ghada Gawdat
Mohamed El Sada
Daniel F. Schorderet
Hana Abou Zeid
37 Retinal Pigment Epithelial Cells: The Unveiled Component in the Etiology of Prpf Splicing Factor-Associated Retinitis Pigmentosa
227(6)
Abdallah Hamieh
Emeline F. Nandrot
38 Genetic Deciphering of Early-Onset and Severe Retinal Dystrophy Associated with Sensorineural Hearing Loss
233(6)
Sabrina Mechaussier
Sandrine Marlin
Josseline Kaplan
Jean-Michel Rozet
Isabelle Perrault
39 Naturally Occurring Inherited Forms of Retinal Degeneration in Vertebrate Animal Species: A Comparative and Evolutionary Perspective
239(6)
Freya M. Mowat
40 RD Genes Associated with High Photoreceptor cGMP-Levels (Mini-Review)
245(6)
Francois Paquet-Durand
Valeria Marigo
Per Ekstrom
41 The Enigma of CRB1 and CRB1 Retinopathies
251(6)
Thomas A. Ray
Kelly J. Cochran
Jeremy N. Kay
42 Update on Inherited Retinal Disease in South Africa: Encouraging Diversity in Molecular Genetics
257(6)
Lisa Roberts
George Rebello
Jacquie Greenberg
Raj Ramesar
43 Emerging Drug Therapies for Inherited Retinal Dystrophies
263(6)
Husvinee Sundaramurthi
Ailfs Moran
Andrea Cerquone Perpetuini
Alison Reynolds
Breandan Kennedy
44 Analysis of the ABCA4 c.[ 2588G<C;5603A<T] Allele in the Australian Population
269(6)
Jennifer A. Thompson
John (Pei-Wen) Chiang
John N. De Roach
Terri L. McLaren
Fred K. Chen
Ling Hoffmann
Isabella Campbell
Tina M. Lamey
45 Retinal Bioenergetics: New Insights for Therapeutics
275(6)
Daniel M. Maloney
Naomi Chadderton
Arpad Palfi
Sophia Millington-Ward
G. Jane Farrar
46 Applications of Genomic Technologies in Retinal Degenerative Diseases
281(8)
Rinki Ratnapriya
Part VI Mechanisms of Degeneration
47 Lipid Signaling in Retinal Pigment Epithelium Cells Exposed to Inflammatory and Oxidative Stress Conditions. Molecular Mechanisms Underlying Degenerative Retinal Diseases
289(6)
Vicente Bermudez
Paula E. Tenconi
Norma M. Giusto
Melina V. Mateos
48 Light Intensity-Dependent Dysregulation of Retinal Reference Genes
295(6)
Christina B. Bielmeier
Sabrina I. Schmitt
Barbara M. Braunger
49 cAMP and Photoreceptor Cell Death in Retinal Degeneration
301(4)
Jason Charish
50 Pathomechanisms of ATF6-Associated Cone Photoreceptor Diseases
305(6)
Wei-Chieh Jerry Chiang
Heike Kroeger
Lulu Chea
Jonathan H. Lin
51 Differential Contribution of Calcium-Activated Proteases and ER-Stress in Three Mouse Models of Retinitis Pigmentosa Expressing P23H Mutant RHO
311(6)
Antonella Comitato
Davide Schiroli
Clara La Marca
Valeria Marigo
52 Peroxisomal Disorders and Retinal Degeneration
317(6)
Yannick Das
Myriam Baes
53 Parthanatos as a Cell Death Pathway Underlying Retinal Disease
323(6)
Scott H. Greenwald
Eric A. Pierce
54 Inner Blood-Retinal Barrier Regulation in Retinopathies
329(6)
Natalie Hudson
Matthew Campbell
55 Oxidative Stress, Diabetic Retinopathy, and Superoxide Dismutase 3
335(6)
Larissa Ikelle
Muna I. Naash
Muayyad R. Al-Ubaidi
56 Bisretinoids: More than Meets the Eye
341(6)
Hye Jin Kim
Janet R. Sparrow
57 Intravitreal Injection of Amyloid β1--42 Activates the Complement System and Induces Retinal Inflammatory Responses and Malfunction in Mouse
347(6)
Ru Lin
Xinyu Fu
Chunyan Lei
Mingzhu Yang
Yiguo Qiu
Bo Lei
58 Persistent Activation of STAT3 Pathway in the Retina Induced Vision Impairment and Retinal Degenerative Changes in Ageing Mice
353(6)
Bernadette Marrero
Chang He
Hyun-Mee Oh
Umegbewe T. Ukwu
Cheng-Rong Yu
Ivy M. Dambuza
Lin Sun
Charles E. Egwuagu
59 High-Throughput Analysis of Retinal Cis-Regulatory Networks by Massively Parallel Reporter Assays
359(6)
Inez Y. Oh
Shiming Chen
60 Pathoconnectome Analysis of Midler Cells in Early Retinal Remodeling
365(6)
Rebecca L. Pfeiffer
James R. Anderson
Daniel P. Emrich
Jeebika Dahal
Crystal L. Sigulinsky
Hope A. B. Morrison
Jia-Hui Yang
Carl B. Watt
Kevin D. Rapp
Mineo Kondo
Hiroko Terasaki
Jessica C. Garcia
Robert E. Marc
Bryan W. Jones
61 Sildenafil Administration in Dogs Heterozygous for a Functional Null Mutation in Pde6a: Suppressed Rod-Mediated ERG Responses and Apparent Retinal Outer Nuclear Layer Thinning
371(6)
Kenneth E. Pierce
Paul G. Curran
Christopher P. Zelinka
Andy J. Fischer
Simon M. Petersen-Jones
Joshua T. Bartoe
62 Role of the PNPLA2 Gene in the Regulation of Oxidative Stress Damage of RPE
377(6)
Preeti Subramanian
S. Patricia Becerra
63 HI)AC Inhibition Prevents Primary Cone Degeneration Even After the Onset of Degeneration
383(6)
Marijana Samardzija
Klaudija Masarini
Marius Ueffing
Dragana Trifunovic
64 Live Imaging of Organelle Motility in RPE Flatmounts
389(6)
Ankita Umapathy
David S. Williams
65 ERG Alteration Due to the rd8 Mutation of the Crbl Gene in Cln3 +/+ rd8-/rd8- Mice
395(6)
Cornelia Volz
Myriam Mirza
Thomas Langmann
Herbert Jagle
66 Autophagy Induction by HDAC Inhibitors Is Unlikely of Retinal Degeneration Caused by P23H Rhodopsin
401(6)
Runxia H. Wen
Aaron D. Loewen
Ruanne Y. J. Vent-Schmidt
Orson L. Moritz
67 Techniques to Quantify cGMP Dysregulation as a Common Pathway Associated with Photoreceptor Cell Death in Retinitis Pigmentosa
407(6)
Paul Yang
Rachel A. Lockard
Hope Titus
68 Hypoxia-Regulated MicroRNAs in the Retina
413(6)
Maya Barben
Ana Bordonhos
Marijana Samardzija
Christian Grimm
69 Bestrophinl: A Gene that Causes Many Diseases
419(6)
Joseph J. Smith
Britta Nommiste
Amanda-Jayne F. Carr
70 Analysis of Damage and Wound Healing in the Retinal Pigmented Epithelium
425(6)
K. J. Donaldson
W. F. Wu
H. Skelton
S. Markand
S. Ferdous
J. Sellers
M. A. Chrenek
I. Gefke
S. M. Kim
J. Rha
K. L. Liao
H. E. Grossniklaus
Y. Jiang
J. Kong
J. H. Boatright
John M. Nickerson
71 Release of Retinal Extracellular Vesicles in a Model of Retinitis Pigmentosa
431(6)
Ayse Sahaboglu
Lorena Vidal-Gil
Javier Sancho-Pelluz
72 GSK-3 Inhibitors: From the Brain to the Retina and Back Again
437(8)
Alonso Sanchez-Cruz
Ana Martinez
Enrique J. de la Rosa
Catalina Hernandez-Sanchez
Part VII Neuroprotection
73 Signaling Mechanisms Involved in PEDF-Mediated Retinoprotection
445(6)
Glorivee Pagan-Mercado
S. Patricia Becerra
74 Initial Assessment of Lactate as Mediator of Exercise-Induced Retinal Protection
451(6)
Jana T. Sellers
Micah A. Chrenek
Preston E. Girardot
John M. Nickerson
Machelle T. Pardue
Jeffrey H. Boatright
75 The Resveratrol Prodrug JC19 Delays Retinal Degeneration in rd10 Mice
457(6)
Lourdes Valdes-Sanchez
Ana B. Garcia-Delgado
Adoration Montero-Sanchez
Berta de la Cerda
Ricardo Lucas
Pablo Penalver
Juan C. Morales
Shorn S. Bhattacharya
Francisco J. Diaz-Corrales
76 A Novel Mechanism of Sigma 1 Receptor Neuroprotection: Modulation of miR-214-3p
463(6)
Jing Wang
Sylvia B. Smith
77 Critical Role of Trophic Factors in Protecting Miiller Glia: Implications to Neuroprotection in Age-Related Macular Degeneration, Diabetic Retinopathy, and Anti-VEGF Therapies
469(8)
Bei Xu
Huiru Zhang
Meili Zhu
Yun-Zheng Le
Part VIII Retinal Cell Biology
78 AMPK May Play an Important Role in the Retinal Metabolic Ecosystem
477(6)
Emily E. Brown
Alfred S. Lewin
John D. Ash
79 Prominin-1 and Photoreceptor Cadherin Localization in Xenopus laevis: Protein-Protein Relationships and Function
483(6)
Brittany J. Carr
Lee Ling Yang
Orson L. Moritz
80 Postmitotic Cone Migration Mechanisms in the Mammalian Retina
489(6)
Livia S. Carvalho
Carta B. Mellough
81 The Role of the Prph2 C-Terminus in Outer Segment Morphogenesis
495(6)
Shannon M. Conley
Muayyad R. Al-Ubaidi
Muna I. Naash
82 The Dynamic and Complex Role of the Joubert Syndrome-Associated Ciliary Protein, ADP-Ribosylation Factor-Like GTPase 13B (ARL13B) in Photoreceptor Development and Maintenance
501(6)
Tanya Dilan
Visvanathan Ramamurthy
83 No Difference Between Age-Matched Male and Female C57BL/6J Mice in Photopic and Scotopic Electroretinogram a- and b-Wave Amplitudes or in Peak Diurnal Outer Segment Phagocytosis by the Retinal Pigment Epithelium
507(6)
Francesca Mazzoni
Tasha Tombo
Silvia C. Finnemann
84 Mitochondrial Gymnastics in Retinal Cells: A Resilience Mechanism Against Oxidative Stress and Neurodegeneration
513(6)
Serena Mirra
Gemma Marfany
85 New Insights into Endothelin Signaling and Its Diverse Roles in the Retina
519(6)
Sabrina I. Schmitt
Christina B. Bielmeier
Barbara M. Braunger
86 Analysis of ATP-Induced Ca2+ Responses at Single Cell Level in Retinal Pigment Epithelium Monolayers
525(6)
Juhana Sorvari
Taina Viheriala
Tanja Ilmarinen
Teemu O. Ihalainen
Soile Nymark
87 PRCD Is a Small Disc-Specific Rhodopsin-Binding Protein of Unknown Function
531(6)
William J. Spencer
Vadim Y. Arshavsky
88 RPE65 Palmitoylation: A Tale of Lipid Posttranslational Modification
537(6)
Sheetal Uppal
Eugenia Poliakov
Susan Gentleman
T. Michael Redmond
89 Studies of the Periciliary Membrane Complex in the Syrian Hamster Photoreceptor
543(8)
Junhuang Zou
Rong Li
Zhongde Wang
Jun Yang
Part IX Stem Cells
90 Induction of Rod and Cone Photoreceptor-Specific Progenitors from Stem Cells
551(6)
Brian G. Ballios
Saeed Khalili
Molly S. Shoichet
Derek van der Kooy
91 A Mini Review: Moving iPSC-Derived Retinal Subtypes Forward for Clinical Applications for Retinal Degenerative Diseases
557(6)
Chloe Cho
Thu T. Duong
Jason A. Mills
92 Restoring Vision Using Stem Cells and Transplantation
563(6)
Elisa Cuevas
Paresh Parmar
Jane C. Sowden
93 Subretinal Implantation of a Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium Monolayer in a Porcine Model
569(6)
Amir H. Kashani
Ana Martynova
Michael Koss
Rodrigo Brant
Dan Hong Zhu
Jane Lebkowski
David Hinton
Dennis Clegg
Mark S. Humayun
94 Flavin Imbalance as an Important Player in Diabetic Retinopathy
575(6)
Tirthankar Sinha
Muayyad R. Al-Ubaidi
Muna I. Naash
Index 581