Tombran-Tink / Barnstable Retinal Degenerations

Biology, Diagnostics, and Therapeutics
1. Auflage 2007
ISBN: 978-1-59745-186-4
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 466 Seiten

Reihe: Ophthalmology Research

This book presents new and noteworthy research into retinal diseases. It focuses on what we currently know about the environment, genetics and mechanisms that lead to retinal degenerations, new diagnostics, and innovative therapeutic modalities to preserve vision. Written by renowned scientific investigators, this innovative collection of treatment strategies and technological discoveries allows for the realistic translation of research into practice.

Autoren/Hrsg.

Tombran-Tink, Joyce

Barnstable, Colin J.

Inhaltsverzeichnis

1;PREFACE;6
2;CONTENTS;11
3;CONTRIBUTORS;14
4;I LIVING WITH RETINAL DEGENERATION;18
4.1;Coping With Retinal Degeneration;19
4.1.1;INTRODUCTION;19
4.1.2;CHAPTER STRUCTURE;19
4.1.3;COPING WITH RETINAL DEGENERATION: JAMES CAPE;20
4.1.4;COPING WITH RETINAL DEGENERATION: GORDON COUSINS;26
5;II DEGENERATIVE DISEASES OF THE RETINA;37
5.1;Epidemiology of Age-Related Macular Degeneration Early in the 21st Century;38
5.1.1;INTRODUCTION;38
5.1.2;CURRENT “GOLD-STANDARD” FOR IDENTIFYING AMD PHENOTYPES;38
5.1.3;PREVALENCE OF AMD Whites;39
5.1.4;INCIDENCE AND PROGRESSION OF AMD Whites;42
5.1.5;RISK FACTORS ASSOCIATED WITH AMD PREVALENCE OR INCIDENCE Genetic Influences;43
5.1.6;IMPACT OF AMD;54
5.1.7;SUMMARY;56
5.1.8;ACKNOWLEDGMENTS;57
5.1.9;REFERENCES;57
5.2;Leber Congenital Amaurosis;75
5.2.1;INTRODUCTION;75
5.2.2;DIFFERENTIAL DIAGNOSIS OF LCA;76
5.2.3;BIOLOGY OF THE LCA GENES AIPL1;78
5.2.4;CRX;81
5.2.5;CRB1;84
5.2.6;GUCY2D;87
5.2.7;RPE65;89
5.2.8;RPGRIP1;93
5.2.9;RDH12;96
5.2.10;SUMMARY;96
5.2.11;ACKNOWLEDGMENTS;97
5.2.12;REFERENCES;97
5.3;Macular Degeneration;105
5.3.1;INTRODUCTION;105
5.3.2;GROWTH FACTOR GENE THERAPY FOR AMD;106
5.3.3;TRANSPLANTATION OF GENETICALLY MODIFIED IRIS PIGMENT EPITHELIAL CELLS;106
5.3.4;ADENOVIRAL VECTORS GENE THERAPY;107
5.3.5;PHARMACOLOGICAL INHIBITION OF THE VEGF IN PATIENTS WITH WET AMD Background;107
5.3.6;VEGF AND ITS RECEPTORS;108
5.3.7;THE ANGIOGENESIS PROCESS: HOW DO NEW VESSELS GROW?;108
5.3.8;ROLE OF VEGF IN PHYSIOLOGICAL AND PATHOLOGICAL ANGIOGENESIS IN AMD;110
5.3.9;CLASSIFICATION OF ANGIOGENESIS INHIBITORS;111
5.3.10;ANTI-ANGIOGENESIS THERAPY FOR EXUDATIVE AMD;113
5.3.11;CONCLUSION;116
5.3.12;ACKNOWLEDGMENTS;116
5.3.13;REFERENCES;116
5.4;Stargardt Disease;118
5.4.1;INTRODUCTION;118
5.4.2;STARGARDT DISEASE;118
5.4.3;GENETIC PREDISPOSITION: THE ABCA4 (ABCR) GENE;120
5.4.4;MOLECULAR DIAGNOSIS;121
5.4.5;FUNCTIONAL STUDIES OF ABCA4;123
5.4.6;EMERGING THERAPEUTIC OPTIONS;123
5.4.7;OUTLOOK;126
5.4.8;ACKNOWLEDGMENTS;127
5.4.9;REFERENCES;127
5.5;X-Linked Juvenile Retinoschisis;132
5.5.1;INTRODUCTION;132
5.5.2;CLINICAL MANIFESTATION;133
5.5.3;CLINICAL DIAGNOSIS OF RS;134
5.5.4;COMPLICATIONS IN RS;135
5.5.5;Differential Diagnosis in RS;135
5.5.6;TREATMENT OPTIONS;136
5.5.7;ISOLATION OF THE RS1 GENE AND STRUCTURAL FEATURES OF ITS GENE PRODUCT;136
5.5.8;SPECTRUM AND MOLECULAR PATHOLOGY OF RS- ASSOCIATED MUTATIONS;136
5.5.9;FUNCTIONAL PROPERTIES OF RETINOSCHISIN The Discoidin Domain and Its Putative Role in Protein Function;139
5.5.10;CONCLUSIONS AND FUTURE DIRECTIONS;144
5.5.11;ACKNOWLEDGMENTS;145
5.5.12;REFERENCES;145
5.6;Retinal Degeneration in Usher Syndrome;149
5.6.1;INTRODUCTION;149
5.6.2;CLINICAL SUBTYPES AND GENETICS;149
5.6.3;VISUAL IMPAIRMENT IN USHER SYNDROME;150
5.6.4;RETINAL FUNCTION OF USHER PROTEINS;151
5.6.5;RETINAL PATHOGENESIS;155
5.6.6;SUMMARY;156
5.6.7;REFERENCES;156
5.7;Mouse Models of RP;161
5.7.1;INTRODUCTION;161
5.7.2;TYPES OF RETINAL DEGENERATION Retinal Degeneration 1 ( Pde6brd1);161
5.7.3;SUMMARY;169
5.7.4;REFERENCES;169
6;III MECHANISMS UNDERLYING RETINAL DEGENERATIONS;174
6.1;The Impact of Diabetes on Neuronal, Glial, and Vascular Cells of the Retina;175
6.1.1;INTRODUCTION;175
6.1.2;GLIAL CELL INVOLVEMENT IN DIABETIC RETINOPATHY;176
6.1.3;NEURONAL CELL LOSS IN DIABETIC RETINOPATHY;178
6.1.4;GANGLION CELLS;179
6.1.5;AMACRINE, BIPOLAR, AND HORIZONTAL CELLS;182
6.1.6;PHOTORECEPTOR CELLS;183
6.1.7;RETINAL PIGMENT EPITHELIUM;183
6.1.8;ENDOTHELIAL CELLS;185
6.1.9;SUMMARY;187
6.1.10;ACKNOWLEDGMENT;188
6.1.11;REFERENCES;188
6.2;Statins and Age-Related Maculopathy;194
6.2.1;AGE-RELATED MACULOPATHY;194
6.2.2;HMG-CoA REDUCTASE INHIBITORS (STATINS);195
6.2.3;BIOLOGICAL PLAUSIBILITY FOR STATINS AS BENEFICIAL FOR ARM;196
6.2.4;EXISTING STUDIES ON CHOLESTEROL-LOWERING MEDICATIONS AND ARM;197
6.2.5;SUMMARY;200
6.2.6;ACKNOWLEDGMENTS;201
6.2.7;REFERENCES;201
6.3;The Role of Drusen in Macular Degeneration and New Methods of Quantification;206
6.3.1;INTRODUCTION;206
6.3.2;DRUSEN CHARACTERISTICS AND SUBTYPES;206
6.3.3;DRUSEN AS A RISK FACTOR;207
6.3.4;DRUSEN COMPOSITION;207
6.3.5;DRUSEN IN OTHER DISEASES;207
6.3.6;PATHOPHYSIOLOGY OF DRUSEN Historical Theories;208
6.3.7;IMAGING;209
6.3.8;AUTOMATED DRUSEN MEASUREMENT BY THE MATHEMATICAL BACKGROUND MODEL The Concept;213
6.3.9;APPLICATION: SEGMENTATION AND CO-LOCALIZATION OF DRUSEN AND AUTOFLUORESCENCE;216
6.3.10;THE FUTURE OF MACULAR IMAGE ANALYSIS;216
6.3.11;REFERENCES;217
6.4;RPE Lipofuscin;221
6.4.1;INTRODUCTION;221
6.4.2;PACKAGING OF LIPOFUSCIN IN THE RPE;222
6.4.3;CHEMICAL COMPOSITION OF RPE LIPOFUSCIN;223
6.4.4;A2E BIOSYNTHETIC PATHWAYS AND MODULATION OF ITS FORMATION;225
6.4.5;SPECTROSCOPY AND FLUORESCENCE IMAGING;229
6.4.6;AGE-DEPENDENCE AND SPATIAL RELATIONSHIPS;230
6.4.7;PHOTOCHEMISTRY;231
6.4.8;ADVERSE EFFECTS OF LIPOFUSCIN ACCUMULATION;232
6.4.9;CLINICAL IMPLICATIONS OF LIPOFUSCIN ACCUMULATION;234
6.4.10;SUMMARY;235
6.4.11;REFERENCES;235
6.5;Genetic Modifiers That Affect Phenotypic Expression of Retinal Diseases;245
6.5.1;INTRODUCTION;245
6.5.2;GENETIC MODIFIERS OF RETINAL DISEASES IN HUMANS;249
6.5.3;GENETIC MODIFIERS OF RETINAL DISEASES IN MICE AND OTHER MODEL ORGANISMS;251
6.5.4;STRATEGIES AND EXAMPLES OF CLONING GENETIC MODIFIERS;254
6.5.5;SUMMARY AND PERSPECTIVES;258
6.5.6;REFERENCES;258
6.6;X-Linked Retinal Dystrophies and Microtubular Functions Within the Retina;264
6.6.1;INTRODUCTION;264
6.6.2;CLINICAL MANIFESTATIONS OF XLRP;265
6.6.3;RP3 TYPE X-LINKED RP AND THE RPGR GENE;266
6.6.4;RPGR Function;267
6.6.5;RP2-TYPE XLRP AND THE RP2 GENE;269
6.6.6;ACKNOWLEDGMENTS;271
6.6.7;REFERENCES;271
6.7;Synaptic Remodeling in Retinal Degeneration;275
6.7.1;INTRODUCTION: COMMON CONSEQUENTIAL EVENTS OF MUTATION- INDUCED ROD- CONE PHOTORECEPTOR DEGENERATION;275
6.7.2;SYNAPTIC ORGANIZATION IN THE OPL AND SIGNALING PATHWAYS OF MAMMALIAN RETINAS;276
6.7.3;RETINAL DEGENERATION IN THE RHODOPSIN P347L TRANSGENIC PIG;278
6.7.4;ECTOPIC SYNAPTOGENESIS IN RETINA OF RHODOPSIN P347L TRANSGENIC PIG;278
6.7.5;ECTOPIC SYNAPTOGENESIS IS A COMMON CONSEQUENTIAL EVENT IN ANIMAL MODELS OF MUTATION- INDUCED RP Ectopic Synaptogenesis in rd Mice;282
6.7.6;SYNAPTIC REMODELING IN OTHER RETINAL DEGENERATION ANIMAL MODELS AND THE UNDERLYING PRINCIPLES OF SYNAPTIC PARTNERING IN THE RETINA;287
6.7.7;IMPLICATIONS FOR PATHOGENESIS OF LATERAL EXTENSIONS OF ROD BIPOLAR CELL DENDRITES;289
6.7.8;CONCLUDING REMARKS;291
6.7.9;REFERENCES;292
7;IV DEVELOPING THERAPEUTIC STRATEGIES FOR RETINAL DEGENERATIVE DISEASES;296
7.1;On The Suppression of Photoreceptor Cell Death in Retinitis Pigmentosa;297
7.1.1;INTRODUCTION;297
7.1.2;APOPTOSIS On the Mechanism of Apoptosis;301
7.1.3;CALCIUM INVOLVEMENT IN APOPTOSIS;304
7.1.4;OXIDATIVE STRESS INVOLVEMENT IN APOPTOSIS;305
7.1.5;TROPHIC FACTORS AND THE POTENTIAL FOR GENE THERAPY;307
7.1.6;ON THE SIGNIFICANCE OF LIGHT-INDUCED RETINAL APOPTOSIS AS A MODEL OF RP;308
7.1.7;ON THE INFLUENCE OF GENETIC AND ENVIRONMENTAL FACTORS ON PHOTORECEPTOR CELL DEATH;309
7.1.8;MODIFIERS OF RP IN HUMANS;310
7.1.9;MODIFIERS OF RP IN MOUSE MODELS;311
7.1.10;CONCLUSION;312
7.1.11;REFERENCES;312
7.2;Cell-Based Therapies to Restrict the Progress of Photoreceptor Degeneration;322
7.2.1;INTRODUCTION;322
7.2.2;ANIMAL MODELS;323
7.2.3;MEASURES OF EFFICACY OF TREATMENT REGIMENS;325
7.2.4;EXPERIMENTAL PROTOCOL;327
7.2.5;DONOR CELLS Freshly Harvested RPE Cells;328
7.2.6;SUMMARY;337
7.2.7;ACKNOWLEDGMENTS;338
7.2.8;REFERENCES;338
7.3;Current Status of IPE Transplantation and Its Potential as a Cell- Based Therapy for Age- Related Macular Degeneration and Retinal Dystrophies;348
7.3.1;INTRODUCTION;348
7.3.2;EVIDENCE FOR RPE PROLIFERATION/MIGRATION OF RPE CELLS IN SUBRETINAL SPACE AND FUNCTIONAL RECOVERY Clinical Observations of a Case;349
7.3.3;COMPARISONS OF CHARACTERISTICS OF RPE AND IPE CELLS AND RESULTS OF SIMULTANEOUS SUBMACULAR SURGERY AND CULTURED AUTOLOGOUS IPE TRANSPLANTATION IN EYES WITH AMD;351
7.3.4;CHARACTERISTICS OF NEUROTROPHIC GENE TRANSFECTED IPE CELLS: BASIC STUDIES;359
7.3.5;OUR THERAPEUTIC STRATEGY FOR RETINAL DYSTROPHIES AND AMD;364
7.3.6;ACKNOWLEDGMENTS;364
7.3.7;REFERENCES;364
7.4;Recent Results in Retinal Transplantation Give Hope for Restoring Vision;368
7.4.1;ABSTRACT;368
7.4.2;INTRODUCTION Retinal Transplantation: A Hope for Incurable Retinal Diseases;368
7.4.3;CLINICAL TRIALS;372
7.4.4;ANIMAL RESEARCH WITH FETAL SHEET TRANSPLANTS Retinal Degeneration Animal Models Used for Transplantation;375
7.4.5;SUMMARY OF RESEARCH ACCOMPLISHMENTS BUILDING THE BASIS FOR CLINICAL TRIALS;380
7.4.6;FUTURE DIRECTIONS;381
7.4.7;ACKNOWLEDGMENTS;381
7.4.8;REFERENCES;382
7.5;Stem Cells and Retinal Transplantation;387
7.5.1;INTRODUCTION;387
7.5.2;RETINAL TRANSPLANTATION: FROM PAST TO PRESENT;388
7.5.3;STEM CELL CHARACTERISTICS;390
7.5.4;RETINAL TRANSPLANTATION OF CNS STEM CELLS;392
7.5.5;CONCLUSIONS;398
7.5.6;REFERENCES;399
7.6;Application of Encapsulated Cell Technology for Retinal Degenerative Diseases;402
7.6.1;THE ENCAPSULATED CELL TECHNOLOGY;402
7.6.2;THERAPEUTIC EFFICACY OF THE NT-501 DEVICE FOR PHOTORECEPTOR PROTECTION;404
7.6.3;PHARMACOKINETICS OF NT-501 DELIVERED CNTF;407
7.6.4;POTENTIAL APPLICATION OF ECT FOR OTHER RETINAL DISEASES Neuroprotection in Glaucoma;408
7.6.5;SUMMARY;411
7.6.6;REFERENCES;411
7.7;Effective Treatment for the Canine RPE65 Null Mutation, a Hereditary Retinal Dystrophy Comparable to Human Leber’s Congenital Amaurosis;415
7.7.1;INTRODUCTION;415
7.7.2;MATERIALS AND METHODS;418
7.7.3;RESULTS;420
7.7.4;DISCUSSION AND CONCLUSION;427
7.7.5;ACKNOWLEDGMENTS;428
7.7.6;REFERENCES;428
7.8;Neuroprotective Factors and Retinal Degenerations;432
7.8.1;INTRODUCTION;432
7.8.2;USING NEUROTRANSMITTERS AND THEIR RECEPTORS TO PROTECT RETINAL GANGLION CELLS FROM GLAUCOMA- ASSOCIATED DEGENERATION;433
7.8.3;STEROIDS AND LIPIDS AS NEUROPROTECTIVE FACTORS FOR RETINAL DEGENERATIONS;434
7.8.4;ANTIOXIDANTS OFFER PROTECTION TO PHOTORECEPTORS: MITOCHONDRIAL UNCOUPLING PROTEINS;435
7.8.5;POLYPEPTIDES THAT PROMOTE SURVIVAL OF NEURONS IN THE CNS;437
7.8.6;NON-NEURONAL RETINAL TARGETS FOR NEUROPROTECTIVE FACTORS;440
7.8.7;DELIVERY OF NEUROPROTECTIVE FACTORS Systemic Delivery;442
7.8.8;SUMMARY AND PROSPECTS;445
7.8.9;REFERENCES;446
7.9;Carbonic Anhydrase Inhibitors as a Possible Therapy for RP17, an Autosomal Dominant Retinitis Pigmentosa Associated With the R14W Mutation, Apoptosis, and the Unfolded Protein Response;454
7.9.1;INTRODUCTION;454
7.9.2;DISCUSSION;454
7.9.3;CONCLUSION;457
7.9.4;REFERENCES;457
7.10;Macular Degeneration - An Addendum;458
8;INDEX;462