Retinal Degenerative Diseases

Name: Retinal Degenerative Diseases
Brand: Springer
Price: 223.63 EUR
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Matthew M. LaVail John Ash Robert E. Anderson Joe G. Hollyfield Christian Grimm(Editor)

Springer (Publisher)

1st Edition

Published on 21. December 2011

LXIV, 864 pages

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978-1-4614-0631-0 (ISBN)

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Content

Intro
Retinal Degenerative Diseases
Preface
About the Editors
Contents
Contributors
Travel Awards
Part I: AMD: Basic Mechanisms, Inflammation and Immunity
Chapter 1: A Window to Innate Neuroimmunity: Toll-Like Receptor-Mediated Cell Responses in the Retina
1.1 Introduction
1.2 TLRs and Neuroimmunity
1.3 TLRs and Age-Related Macular Degeneration
1.4 Short Interfering RNA-Based Drugs Activate TLR3 Pathways
References
Chapter 2: Autoimmune Biomarkers in Age-Related Macular Degeneration: A Possible Role Player in Disease Development and Progression
2.1 Introduction
2.2 Evidence in Favor of a Role for Autoimmunity in AMD Pathogenesis
2.3 Preliminary Results from Our Research Support the Role of Autoimmunity in AMD
2.4 Experimental Framework and Future Directions
References
Chapter 3: Local Vs. Systemic Mononuclear Phagocytes in Age-Related Macular Degeneration and Their Regulation by CCL2-CCR2 and CX3CL1-CX3CR1 Chemokine Signalling
3.1 Introduction
3.2 Mononuclear Phagocytes Comprise a Heterogeneous Population of Systemic and Local Innate Immune Cells
3.3 Activation of Mononuclear Phagocytes Is Controlled by Signals from the Microenvironment
3.4 Evidence of the Involvement of Myeloid Cells in the Pathophysiology of AMD
3.5 The Identification of the Chemokine Receptor CX3CR1 as a Risk Factor for AMD
3.6 CCR2 and CX3CR1 Signalling Contribute Differentially to the Recruitment of Monocyte Subsets to the Retina and Also Control Local Microglia Responses
3.7 Future Directions
References
Chapter 4: Sublytic Membrane-Attack-Complex Activation and VEGF Secretion in Retinal Pigment Epithelial Cells
4.1 Introduction
4.2 Results
4.3 Discussion
References
Chapter 5: Complement Activation in Retinal Degeneration
5.1 Introduction
5.2 Methods
5.3 Results
5.4 Discussion
References
Chapter 6: Microglia in the Outer Retina and Their Relevance to Pathogenesis of Age-Related Macular Degeneration
6.1 Introduction
6.2 AMD Pathology in the Retinochoroidal Interface
6.3 Microglia-RPE Interactions in the Outer Retina
6.4 Therapeutic Perspectives
References
Chapter 7: Lutein or Zeaxanthin Supplementation Suppresses Inflammatory Responses in Retinal Pigment Epithelial Cells and Macrophages
7.1 Introduction
7.2 Materials and Methods
7.2.1 Materials
7.2.2 Experiments with Animals
7.2.3 Cell Culture and Treatments
7.3 Results
7.3.1 Supplementation with Lutein or Zeaxanthin to RPE Reduces Basal Level and LPS-Induced Secretion of IL-6 and IL-8
7.3.2 Lutein Supplementation to Primary Macrophage Cultures Suppresses LPS-Induced Secretion of IL-6 and TNF a
7.3.3 Macrophages Isolated from Lutein or Zeaxanthin Supplemented Mice Produce Less IL-6 and TNF a upon LPS Stimulation
7.4 Discussion
References
Chapter 8: Exploring the Potential Role of the Oxidant-Activated Transcription Factor Aryl Hydrocarbon Receptor in the Pathogenesis of AMD
8.1 Introduction
8.2 Oxidant Injury of RPE Cells Due to Cigarette Smoke
8.3 RPE Cellular Response to Oxidant Injury
8.4 Aryl Hydrocarbon Receptor
8.4.1 AhR Regulates Cellular Oxidative Stress Response
8.4.2 AhR Regulates Proteosomal Degradation
8.5 Potential Role for AhR in AMD Pathogenesis?
References
Chapter 9: Common Mechanisms for Separate Maculopathies?
9.1 Introduction
9.2 Shared Protein Networks in Common and Rare Maculopathies
9.3 Pathomechanisms of Maculopathies, Modifiable Risk Factors
9.4 The Role of the Extracellular Matrix in the Pathomechanism of Maculopathies
References
Chapter 10: The Role of Amyloid- b in Retinal Degeneration
10.1 Physiopathology of Age-Related Macular Degeneration
10.2 Amyloid- b Is a Component of Drusen
10.3 Amyloid- b Impairs RPE Cell Structure and Function
10.4 Amyloid- b Is Cytotoxic for the Neural Retina
10.5 Amyloid- b Is Proinflammatory in the Retina
10.6 Conclusions
References
Chapter 11: Molecule-Specific Imaging and Quantitation of A2E in the RPE
11.1 Introduction
11.2 Materials and Methods
11.2.1 RPE Tissue Preparation
11.2.2 MALDI Imaging
11.2.3 Quantitation of A2E
11.3 Results
11.3.1 Spatial Localization of A2E in Murine RPE
11.3.2 Quantitation of A2E
11.3.3 A2E Oxidation Sites
11.4 Discussion
References
Chapter 12: Autophagy in the Retina: A Potential Role in Age-Related Macular Degeneration*
12.1 Introduction
12.2 Molecular Events in the Autophagy Process
12.3 Signaling Mechanisms in Autophagy
12.4 Autophagy in the Neural Retina
12.5 Autophagy in the RPE
12.6 The Association Between Autophagy and AMD
12.7 Conclusion
References
Part II: Neuroprotection, Drugs and Novel Protective Therapies
Chapter 13: Regeneration of Cone Outer Segments Induced by CNTF
13.1 Introduction
13.2 Materials and Methods
13.3 Results
13.3.1 Loss of COS in Early Stages of Cone Degeneration
13.3.2 CNTF Promotes COS Regeneration
13.4 Discussion
References
Chapter 14: Glucocorticoid-Dependent Mechanisms in Photoreceptor Survival
14.1 Introduction
14.2 Materials and Methods
14.3 Results
14.3.1 GRs in Control and Light-Exposed Retinas
14.3.2 Rhodopsin
14.3.3 Activation of Caspase-3
14.4 Discussion
References
Chapter 15: HDAC Inhibition Prevents Rd1 Mouse Photoreceptor Degeneration
15.1 Introduction
15.2 Materials and Methods
15.2.1 Animals
15.2.2 In Vitro Retinal Explant Cultures
15.2.3 HDAC Assay
15.2.4 TUNEL and Immunostaining
15.3 Results
15.3.1 Study of Expression and Activity of HDACs in wt and rd1 Retina
15.3.2 HDAC I/II Inhibitors Protect rd1 Photoreceptors Regulating PARP Activity
15.4 Discussion
References
Chapter 16: Neuroprotective Dose Response in RCS Rats Implanted with Microphotodiode Arrays
16.1 Introduction
16.2 Materials and Methods
16.2.1 Implantation of RCS Rats with MPAs
16.2.2 Light Dosing
16.2.3 Retinal Function Testing
16.2.4 Morphological Assessment of Photoreceptor Numbers
16.3 Results
16.3.1 Effects of Light Exposure on Retinal Function in Implanted RCS Rats
16.3.2 Effect of Light Exposure on Photoreceptor Survival in Implanted RCS Rats
16.4 Discussion
References
Chapter 17: Treatment with 670-nm Light Protects the Cone Photoreceptors from White Light-Induced Degeneration
17.1 Introduction
17.2 Materials and Methods
17.3 Results
17.3.1 Effects of 670-nm Light on Bright Light-Induced Photoreceptor Cell Death
17.3.2 670-nm Light Mitigates Loss of Outer Segments Following Photic Injury
17.3.3 Regulation of Cone Opsin Gene by 670-nm Light
17.3.4 670-nm Light Maintains Retinal Function Following Photic Injury
17.4 Discussion
References
Chapter 18: Dark-Rearing the rd10 Mouse: Implications for Therapy
18.1 Introduction
18.2 Methods
18.2.1 Mice
18.2.2 Electroretinography
18.2.3 Immunolabeling and Imaging
18.2.4 Quantitative Real-Time PCR
18.3 Results
18.3.1 Preservation of Function Until PNM3 in the DR-rd10 Mouse
18.3.2 Immunohistochemical Analysis of the Effect of DR on rd10 Retinal Remodeling
18.3.3 QrtPCR Analysis of Candidate Retinal Genes
18.4 Discussion
References
Chapter 19: Intravitreal Injection of Erythropoietin Glycosylation Analogs Does Not Protect Rod Photoreceptor Cells from Light-Induced Damage
19.1 Introduction
19.2 Materials and Methods
19.2.1 Light Exposure
19.2.2 Intravitreal Injection
19.2.3 ERG Recording and Outer Nuclear Layer Thickness Measurement
19.3 Results
19.4 Discussion
References
Chapter 20: Relieving Bottlenecks in RNA Drug Discovery for Retinal Diseases
20.1 Introduction
20.2 Materials and Methods
20.3 Variables in RDD
20.3.1 Agents of PTGS
20.3.2 Validating Appropriate Disease Target mRNAs
20.3.3 Target mRNA Structure and Determinations of Accessibility
20.3.4 Screening Large Numbers of PTGS Agents to Identify a Lead Candidate
20.3.5 Optimizing the Lead Candidate
20.3.6 The Vector, PTGS Expression Construct, and Animal Testing
20.3.7 Appropriate Targets (Human)
20.4 Conclusions
References
Chapter 21: On Further Development of Barrier Modulation as a Technique for Systemic Ocular Drug Delivery
21.1 Introduction
21.2 Therapeutic Delivery Across the iBRB
21.3 The oBRB and Its Potential in Barrier Modulation
21.4 Closing Remarks
References
Chapter 22: An Application for Mammalian Optic Nerve Repair by Fish Regeneration-Associated Genes
22.1 Introduction
22.2 IGF-I
22.3 nNOS
22.4 TG
22.5 Purpurin
22.6 Future Study for Overcoming Mammalian CNS Injury
References
Chapter 23: The Mechanism of Fenretinide (4-HPR) Inhibition of b -carotene Monooxygenase 1. New Suspect for the Visual Side Effects of Fenretinide
23.1 Introduction
23.2 Materials and Methods
23.2.1 Constructs
23.2.2 Protein Expression and Enzyme Assays
23.2.3 HPLC Analysis of Retinoids and Carotenoids
23.2.4 Synthesis of Fenretinine, 15-[(4-Hydroxyphenyl)Amino]Retinal (1)
23.2.5 Tertiary Structure Modeling and Molecular Docking
23.3 Results
23.3.1 Fenretinide is a Potent Inhibitor of BCMO1
23.3.2 Fenretinide Demonstrates Noncompetitive Inhibition Behavior
23.3.3 Fenretinide Does Not Inhibit Catalytic Activity of BCMO1?337-346 Mutant
23.3.4 Amine Analog of Fenretinide (Fenretinine) Is Not an Inhibitor of BCMO1
23.4 Discussion
References
Part III: Gene Therapy
Chapter 24: Gene Augmentation Trials Using the Rpe65-Deficient Dog: Contributions Towards Development and Refinement of Human Clinical Trials
24.1 Introduction
24.2 Gene Therapy Proof-of-Principle Trials in Rpe65-Deficient Dogs
24.3 Phase I/II Clinical Trials in LCAII Patients
24.4 Safety and Efficacy of Treatment of the Second Eye of Rpe65-Deficient Dogs
References
Chapter 25: Gene Therapy Restores Missing Cone-Mediated Vision in the CNGA3 -/- Mouse Model of Achromatopsia
25.1 Introduction
25.2 Materials and Methods
25.2.1 rAAV Production Vectors and Subretinal rAAV Injections
25.2.2 Electrophysiological Analysis
25.2.3 Immunohistochemistry
25.2.4 Behavior
25.3 Results
25.4 Discussion
References
Chapter 26: Functional Rescue of P23H Rhodopsin Photoreceptors by Gene Delivery
26.1 Introduction
26.2 Materials and Methods
26.2.1 Animals
26.2.2 Transient Transfection of HeLa Cells and Immunohistochemistry
26.2.3 ERG
26.2.4 Histology
26.3 Results
26.3.1 Functional Preservation of P23H RHO Photoreceptors as a Result of Overexpression of Mouse RHO 301
26.3.2 Functional Preservation of P23H RHO Photoreceptors as a Result of Increased Expression of Human BiP/Grp78
26.3.3 Preservation of Retinal Integrity in P23H RHO Rats as a Result of Overexpression of Human BiP/GRP78
26.3.4 Elevation of BiP Protein Level Does Not support the Trafficking of P23H RHO to the Cell Membrane
26.3.5 Functional Preservation of P23H RHO Photoreceptors as a Result of Overexpression of HSF1
26.4 Discussion
References
Chapter 27: Gene Delivery of Wild-Type Rhodopsin Rescues Retinal Function in an Autosomal Dominant Retinitis Pigmentosa Mouse Model
27.1 Introduction
27.2 Materials and Methods
27.2.1 RHO301 Gene Cloning
27.2.2 Experiment with Animal Models
27.2.3 Electroretinography (ERG)
27.2.4 Histological Analysis for the Outer Nuclear Layer
27.3 Results
27.3.1 Expression of AAV-Delivered RHO301
27.3.2 Retinal Structure Integrity in AAV Gene-Delivered P23H Mice
27.3.3 Rescued Retinal Function Observed in AAV-RHO301-Injected P23H Eyes
27.4 Discussion
References
Chapter 28: Retinal Degeneration and Cellular Suicide
28.1 Programmed Cell Death Pathways
28.2 Cell Death in Inherited Retinal Dystrophies
28.3 Cell Death in Retinal Damage Models
28.4 Retina Rescue by Blocking PCD
28.5 Looking into the Future
References
Chapter 29: Suppression of rds Expression by siRNA and Gene Replacement Strategies for Gene Therapy Using rAAV Vector
29.1 Introduction
29.2 Materials and Methods
29.2.1 Cell Transfection
29.2.2 RNA Isolation and Semiquantitative Real-Time PCR
29.2.3 AAV Production
29.2.4 Subretinal Injection
29.2.5 Electroretinogram
29.2.6 Statistical Analysis
29.3 Results
29.3.1 Synthetic siRNAs Targeted to rds Reduces Transduction In Vitro in HEK-293 Cells
29.3.2 Effect of siRNA Directed to rds In Vivo in Photoreceptors by rAAV-5 Vector
29.3.3 Construction of rds Resistant to siRNA
29.3.4 Proof of Principal for Combination Therapy for rds Using AAV Vector in Photoreceptors In Vivo
29.4 Discussion
References
Chapter 30: Silencing the Expression of CTRP5 / C1QTNF5 and ELOVL4 Genes by Small Interfering RNA
30.1 Introduction
30.2 Materials and Methods
30.2.1 siRNA Designing
30.2.2 Cell Culture and Transfection of siRNA
30.2.3 Quantitative Real-Time PCR
30.2.4 Immunofluorescence Analysis of Transfected Cos-7 Cells
30.3 Results
30.3.1 siRNA-Mediated Suppression of ELOVL4 mRNA
30.3.2 siRNA Mediated Knockdown of CTRP5/Ctrp5
30.4 Discussion
References
Chapter 31: Gene Therapy Strategies for Usher Syndrome Type 1B
31.1 Introduction
31.2 MYO7A Gene
31.3 Myo7a -Mutant Mice
31.4 Lentivirus-Mediated Gene Therapy
31.5 AAV-Mediated Gene Therapy
31.6 Conclusion: The Best Strategy for Usher 1B Gene Therapy?
References
Part IV: Blood Vessels, Angiogenesis, and Neovascularization
Chapter 32: Neovascularization: Ocular Diseases, Animal Models and Therapies
32.1 Introduction
32.2 Neovascular Ocular Diseases
32.2.1 Age-Related Macular Degeneration
32.2.2 Retinopathy of Prematurity
32.2.3 Diabetic Retinopathy
32.3 Animal Models
32.3.1 Choroidal Neovascularization
32.3.2 Vldlr
32.3.3 Vascular Endothelial Growth Factor
32.3.4 Ins2 Akita
32.3.5 Ins2 Akita VEGF
32.3.6 Oxygen Induced Retinopathy
32.4 Therapeutic Treatment of Ocular Neovascular Diseases
32.4.1 Targeting Pathology and Angiogenic Pathways
32.4.2 Targeting VEGF-Dependent Pathway
32.4.3 Nanomedicine
32.4.4 Regenerative Medicine
32.5 Conclusion
References
Chapter 33: Retinal Neovascular Disorders: Mouse Models for Drug Development Studies
33.1 Introduction
33.2 Proliferative Diabetic Retinopathy
33.3 Retinopathy of Prematurity
33.4 Age-Related Macular Degeneration
33.5 Genetic Mouse Models for Neovascularization
33.6 Nongenetic Models for Neovascularization
33.7 Use of Mouse Models for Neovascularization in Preclinical Drug Testing
33.8 Conclusion
References
Chapter 34: A Review and Update on the Molecular Basis of Pathogenesis of Sorsby Fundus Dystrophy
34.1 Introduction
34.2 Clinical Manifestations of SFD and Therapeutic Intervention
34.3 Mutation Spectrum of TIMP3 in SFD
34.4 Advances in the Elucidation of the Pathogenesis of SFD
34.4.1 Molecular Characteristics of Mutant TIMP3
34.4.2 Clues from Animal Models
34.4.3 Molecular Mechanisms of Angiogenesis in SFD
34.5 TIMP3 and AMD
References
Chapter 35: The Importance of Hypoxia-Regulated, RPE-Targeted Gene Therapy for Choroidal Neovascularization
35.1 Introduction
35.2 Constitutive vs. Regulated Expression
35.3 RPE-Specific Promoters
35.4 Hypoxia-Regulated Expression
35.5 Effectiveness of Endostatin
35.6 Conclusions
References
Chapter 36: What Is the Role of CCR3 in Choroidal Neovascularization?
36.1 Introduction
36.2 Materials and Methods
36.2.1 Animals and Subretinal Injection of Matrigel
36.2.2 Visualization of Blood Vessels and Measurement of CNV
36.3 Results
36.3.1 Development of CNV in the Matrigel Model
36.3.2 CCR3 Targeting and CNV Development in Rats and Mice
36.4 Discussion
References
Chapter 37: Intermittent But Not Constant High Glucose Induces ER Stress and Inflammation in Human Retinal Pericytes
37.1 Introduction
37.2 Materials and Methods
37.2.1 Materials
37.2.2 Cell Culture
37.2.3 Western Blot Analysis
37.2.4 Quantification of MCP-1 Secretion in Pericytes
37.2.5 Statistical Analysis
37.3 Results
37.3.1 High Glucose Suppresses GRP78 Expression in HRP
37.3.2 Intermittent But Not Constant High Glucose Activates ATF4/CHOP and Increases MCP-1 Secretion in HRP
37.3.3 Inhibition of ER Stress by Chemical Chaperones Alleviates Inflammatory Cytokine Expression in HRP Exposed to Intermittent High Glucose
37.4 Discussion
References
Chapter 38: Regulation of Retinal Vascular Permeability by Betacellulin
38.1 Introduction
38.2 Betacellulin: Structure and Expression
38.3 Biological Function of BTC
38.4 Betacellulin Induces Angiogenesis
38.5 Role of Betacellulin in the Retina in Diabetes
38.6 Future Vision
References
Chapter 39: Presence of RPE-Produced VEGF in a Timely Manner Is Critical to Choroidal Vascular Development
39.1 Introduction
39.2 Methods
39.2.1 Animal Experiments
39.2.2 Quantification of Choroidal Vascular Density
39.3 Results
39.3.1 Choroidal Vascular Density
39.3.2 Retinal Integrity
39.4 Discussion
References
Chapter 40: Vasohibin-1 and Retinal Pigment Epithelium
40.1 Introduction
40.2 Methods
40.2.1 RPE Preparation
40.2.2 Real-Time RPE Impedance Analysis and MTS Assay
40.2.3 Extraction of mRNA, cDNA Generation, Reverse-Transcriptase, and Real-Time Polymerase Chain Reaction (RT-PCR)
40.2.4 Western Blot Analysis for Vasohibin-1 and VEGF
40.3 Results
40.3.1 Vasohibin-1 Expression
40.3.2 RPE Dynamics and Proliferation by Vasohibin-1
40.4 Discussion
References
Part V: Genotype/Phenotype
Chapter 41: Polymorphic Variation of RPGRIP1L and IQCB1 as Modifiers of X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR
41.1 Introduction
41.2 Materials and Methods
41.2.1 Patients and Clinical Assessment
41.2.2 Genotyping Candidate Modifier Loci
41.2.3 Data Analysis
41.3 Results
41.3.1 Phenotypic Heterogeneity Between and Within Families
41.3.2 Modifier SNPs
41.4 Discussion
References
Chapter 42: RPGRIP1 and Cone-Rod Dystrophy in Dogs
42.1 Introduction
42.2 Focus on the RPGRIP1 : What Makes It Special?
42.3 Characterization of the RPGRIP1-Associated Protein Network
42.3.1 RPGRIP1 Is a Component of the Transport Network for Cilia Assembly
42.3.2 RPGRIP1 Involvement in Regulating Cytoskeleton Dynamics and Ciliogenesis
42.3.3 Components of Molecular Networks Regulating Cellular Transport and Cytoskeleton Dynamics Show Connection with Visual Pathway
42.4 Dogs with Retinal Degeneration Show Significant Phenotypic Variation with RPGRIP1 Mutation Ins44
References
Chapter 43: High-Throughput Approaches for the Genetic Diagnosis of Retinal Dystrophies
43.1 Introduction
43.2 Direct Molecular Diagnosis of Retinal Dystrophies
43.2.1 Mutation Screening Chips
43.2.2 Resequencing Chips
43.2.3 Next-Generation Sequencing of Target Genes
43.3 Indirect Molecular Diagnosis of Retinal Dystrophies
43.3.1 Homozygosity Mapping
43.3.2 Cosegregation SNP-Chips
43.4 Optimized Multitiered Strategy for Efficient Molecular Diagnosis
43.5 Future Venues and Concluding Remarks
References
Chapter 44: Genes and Mutations in Autosomal Dominant Cone and Cone-Rod Dystrophy
44.1 Introduction
44.2 Materials and Methods
44.2.1 Patients and Clinical Examinations
44.2.2 Genetic Analyses
44.3 Results
44.3.1 Mutation Spectrum
44.4 Discussion
References
Chapter 45: The Power of Homozygosity Mapping: Discovery of New Genetic Defects in Patients with Retinal Dystrophy
45.1 Introduction
45.1.1 Homozygosity Mapping
45.2 The Efficacy of Homozygosity Mapping in Different Types of Families and Populations
45.2.1 Consanguineous vs. Nonconsanguineous Families
45.2.2 Successfulness Based on Population Composition
45.3 Conclusions
45.3.1 Strengths, Limitations, and Future Perspectives of Homozygosity Mapping
References
Chapter 46: Development and Validation of a Canine-Specific Profiling Array to Examine Expression of Pro-apoptotic and Pro-survival Genes in Retinal Degenerative Diseases
46.1 Introduction
46.2 Materials and Methods
46.2.1 Development of the Canine-Specific qRT-PCR Array
46.2.2 Validation of the qRT-PCR Array Using Madin-Darby Canine Kidney (MDCK) Cells
46.2.2.1 Cell Culture
46.2.2.2 Assessment of Cellular Viability
46.2.2.3 qRT-PCR Analysis
46.3 Results
46.4 Discussion and Conclusions
References
Chapter 47: The Chromosome 10q26 Susceptibility Locus in Age-Related Macular Degeneration
47.1 Introduction
47.2 Unravelling the Genetic Association Locus in Chromosomal Region 10q26
47.3 The Contribution of ARMS2 to the AMD Association in Chromosomal Region 10q26
47.4 The Potential Role of HTRA1 in AMD
References
Chapter 48: Congenital Stationary Night Blindness: Mutation Update and Clinical Variability
48.1 Introduction
48.2 Methods
48.2.1 Subjects
48.2.2 Analyses
48.2.2.1 Genetic Analysis
48.2.2.2 Statistical Analysis
48.3 Results
48.3.1 Genetic Analysis
48.3.2 Clinical Variability
48.4 Discussion
48.5 Conclusions
References
Chapter 49: Serum Biomarkers and Trafficking Defects in Peripheral Tissues Reflect the Severity of Retinopathy in Three Brothers Affected by Choroideremia
49.1 Introduction
49.2 Methods
49.2.1 Characterization of the Patient Population
49.2.2 Confocal Microscopy and FACS Analysis on Phagocytosing CD14+ Monocyte Population from CHM Patients and Controls
49.3 Results
49.3.1 Clinical Variation between the Members of the CHM Affected Family
49.3.2 Clinical and Functional Variability Between the Individuals Carrying the Same CHM Mutation
49.4 Discussion
References
Part VI: New Animal Models of Retinal Degeneration
Chapter 50: Translational Vision Research Models Program
50.1 Introduction
50.2 Materials and Methods
50.2.1 Origins of Mice and Husbandry
50.2.2 Clinical Evaluation and Electroretinography
50.2.3 Genetic Mapping and Mutational Analysis
50.2.4 Histological Analysis
50.3 Results and Discussion
50.3.1 A New Mutation in Phosphodiesterase 6A, cGMP-Specific, Rod, Alpha (Pde6a)
50.3.2 A New Mutation in Tubby-Like Protein 1
50.3.3 A New Mutation in Rhodopsin
50.4 Summary
References
Chapter 51: Zebrafish: A Model System for the Investigation of Novel Treatments for Retinal Disease
51.1 Introduction
51.2 Morphological and Embryological Features
51.3 Zebrafish Genetic Resources
51.3.1 Genetic Screens
51.3.2 Mutant Strain Repositories
51.4 Functional Assessment in Zebrafish
51.5 Drug Discovery
51.6 Conclusion
References
Chapter 52: Retinal Degeneration in the Fly
52.1 Introduction
52.2 The Compound Eye and Phototransduction
52.3 Genetic Screens Identify Retinal Degeneration Loci
52.4 Retinal Degenerations in Flies and Humans
52.5 Summary
References
Chapter 53: Looking into Eyes: Rhodopsin Pathologies in Drosophila
53.1 Introduction
53.2 The Dark Side of Rhodopsin
53.3 Pathogenic Mechanisms Underlying RD in Drosophila
53.3.1 Abnormalities in the PT Cascade
53.3.2 Altered Rh1 Endocytosis and Autophagy
53.3.3 Impaired Rh1 Maturation, Trafficking, and Proteasomal Clearance
53.3.4 Pathways to Cell Death in RD
53.4 Conclusions
References
Chapter 54: Müller Glia as a Source of Neuronal Progenitor Cells to Regenerate the Damaged Zebrafish Retina
54.1 Models of Retinal Damage in Zebrafish
54.2 Regeneration of the Light-Damaged Zebrafish Retina
54.3 Induction of Müller Glial Proliferation in the Light-Damaged Zebrafish Retina
54.4 Transcription Factors Required for Maximal Müller Glial Cell Proliferation
54.5 Proteins That Are Required for Neuronal Progenitor Cell Proliferation
54.6 Future Directions
References
Chapter 55: The Genetics of Outer Segment Morphogenesis in Zebrafish
55.1 Introduction
55.1.1 Photoreceptor Outer Segments
55.1.2 Significance of Photoreceptor Outer Segments
55.1.3 Study of Photoreceptor Outer Segment Morphogenesis in Zebrafish
55.2 Zebrafish Mutant Screens
55.3 Zebrafish Outer Segment Mutants
55.3.1 Mutations in Genes Encoding Phototransduction Proteins
55.3.2 Mutations in Intracellular Trafficking Genes
55.3.2.1 Intraflagellar Transport Particle B proteins
55.3.2.2 Microtubule-Dependent Molecular Motors
55.3.2.3 Membrane Transport
55.3.3 Mutations in Genes Encoding Structural Proteins
55.3.4 Mutations in Genes Encoding Transcription Factors
55.3.5 Other Outer Segment Mutants
55.4 Conclusion
References
Chapter 56: Factor XIIIA Induction in the Retina and Optic Nerve After Optic Nerve Lesion in Goldfish
56.1 Introduction
56.2 Materials and Methods
56.2.1 Experiment with Animals
56.2.2 Cloning of Goldfish Neural Factor XIIIA
56.2.3 In Situ Hybridization
56.2.4 Retinal Explant Culture
56.3 Results
56.3.1 Changes in Factor XIIIA Gene Expression in the Retina and Optic Nerve After Optic Nerve Injury
56.3.2 Recombinant Factor XIIIA Protein Clearly Induced Neurite Outgrowth
56.4 Discussion
References
Part VII: Analysis of Retinal Degeneration by Imaging and Functional Testing
Chapter 57: Imaging the Photoreceptor Mosaic with Adaptive Optics: Beyond Counting Cones
57.1 Introduction
57.2 Materials and Methods
57.3 Results
57.3.1 Case 1
57.3.2 Case 2
57.3.3 Case 3
57.4 Discussion
References
Chapter 58: Baseline Imaging Reveals Preexisting Retinal Abnormalities in Mice
58.1 Introduction
58.2 Materials and Methods
58.2.1 Animal Models
58.2.2 Imaging Procedures
58.2.3 Histology
58.3 Results
58.4 Discussion
References
Chapter 59: Correlation Between Spectral Domain OCT Retinal Nerve Fibre Layer Thickness and Multifocal Pattern Electroretinogram in Advanced Retinitis Pigmentosa
59.1 Introduction
59.2 Materials and Methods
59.2.1 Study Population
59.2.2 Electrophysiological Recordings
59.2.3 Retinal Nerve Fibre Layer Imaging
59.3 Results
59.3.1 Basic Characteristics of Study Cohort
59.3.2 Inner Retina Structure-Function Relation
59.4 Discussion
References
Chapter 60: Imaging Human Postmortem Eyes with SLO and OCT
60.1 Introduction
60.2 Materials and Methods
60.2.1 Tissue Preparation
60.2.2 Bright-Field Macroscopic Imaging
60.2.3 Scanning Laser Ophthalmoscope
60.2.4 Optical Coherence Tomography
60.3 Results
60.3.1 Normal Retina
60.3.2 Macular Hole
60.3.3 RPE Detachment
60.3.4 AMD Retina
60.3.5 RP Retina
60.4 Discussion
References
Chapter 61: In Vivo Assessment of Rodent Retinal Structure Using Spectral Domain Optical Coherence Tomography
61.1 Introduction
61.2 Materials and Methods
61.2.1 Animals
61.2.2 Retinal Imaging
61.2.3 Histology
61.3 Results
61.4 Discussion
References
Chapter 62: Rod Photoreceptor Temporal Properties in Retinal Degenerative Diseases
62.1 Introduction
62.2 Materials and Methods
62.2.1 Subjects
62.2.2 Evaluation of the Rod Inactivation Kinetics Using Paired-Flash ERG
62.3 Results
62.3.1 Rod Photoresponse Recovery Kinetics in RDDs
62.3.2 T sat Is Correlated with Dark-Adapted Rod Amplitude in adRP
62.4 Discussion
References
Chapter 63: ERG Critical Flicker Frequency Assessment in Humans
63.1 Introduction
63.2 Materials and Methods
63.2.1 Subject Selection and Preparation
63.2.2 ERG Protocol
63.3 Results
63.3.1 Scotopic CFF
63.3.2 Photopic CFF
63.4 Discussion
References
Part VIII: Mechanisms of Retinal Degeneration
Chapter 64: Biology of Retinoschisin
64.1 Introduction
64.2 RS1 Gene and Protein
64.3 RS1 Interactions
64.4 X-Linked Retinoschisis Mutations
64.5 Clinical Pathology
64.6 Molecular Pathology
64.7 Prospects for Gene Therapy
References
Chapter 65: Transcriptome Analyses to Investigate the Pathogenesis of RNA Splicing Factor Retinitis Pigmentosa
65.1 Introduction
65.2 The Retinal Pigment Epithelium Is the Primary Tissue Affected by Mutations in the Pre-mRNA Processing Factors 3, 8, and 31
65.3 Identifying Aberrantly Spliced Transcripts Using Next-Generation Sequencing
65.3.1 Next-Generation Sequencing Platforms
65.3.2 An Overview of RNA-Seq
65.3.3 Bioinformatic Analysis of RNA-Seq Data
65.4 RNA-Seq Analyses of RNA Splicing Factor Mutant Mice
65.5 Future Experimental Approaches
References
Chapter 66: The Role of the X-linked Retinitis Pigmentosa Protein RP2 in Vesicle Traffic and Cilia Function
66.1 Introduction
66.2 RP2 Structure
66.3 RP2 Cilia Localisation and Function
66.4 New RP2 Interaction Partners
66.5 Conclusions
References
Chapter 67: Caenorhabditis elegans as a Model Organism for Ciliopathies and Related Forms of Photoreceptor Degeneration
67.1 Introduction
67.2 C. elegans BBS Proteins Play a Role in IFT Transport
67.3 BBS Proteins Function in RPE Cells
67.4 C. elegans Have Phototransduction Components
67.5 Is C. elegans a Good Animal Model to Study Photoreceptor Degeneration?
References
Chapter 68: Towards a Pathological Mechanism for IMPDH1-Linked Retinitis Pigmentosa
68.1 Introduction
68.2 IMPDH and the Retina
68.3 IMPDH Structure and Function
68.4 Retinal Splice Variants
68.5 IMPDH and Translation
68.6 Summary
References
Chapter 69: Calpain and Photoreceptor Apoptosis
69.1 Introduction
69.2 Calpain Activation
69.3 Light Ablation Model
69.4 Systemic Delivery of Calpain Inhibitors
69.5 Conclusion
References
Chapter 70: Ceramide Signaling in Retinal Degeneration
70.1 Introduction
70.2 An Overview of Ceramide Metabolism in the Cell
70.3 Ceramide in Photoreceptor Apoptosis
70.4 Ceramide Signaling in RPE Cell Death
70.5 Conclusion
References
Chapter 71: Endoplasmic Reticulum-Associated Degradation (ERAD) of Misfolded Glycoproteins and Mutant P23H Rhodopsin in Photoreceptor Cells
71.1 The Endoplasmic Reticulum: Protein Folding and Quality Control
71.2 Recognition Misfolded Proteins in the ER
71.3 From Quality Control to Dislocation for ERAD
71.4 Cytosolic Events of ERAD
71.5 ERAD in Retinitis Pigmentosa
References
Chapter 72: Protein Misfolding and Potential Therapeutic Treatments in Inherited Retinopathies
72.1 Introduction
72.2 Protein Misfolding in Photoreceptor Cells
72.3 Therapeutic Strategies for Inhibiting Protein Aggregation and Related Toxicity
72.3.1 Inhibition of Conformational Shift
72.3.2 Enhancing Chaperone Activities
72.3.3 Inhibition of Factors Mediating Cell Toxicity
72.3.4 Gene Therapy
72.4 Conclusions
References
Chapter 73: Development of a Cellular Model of Rod Opsin Retinitis Pigmentosa
73.1 Introduction
73.2 Materials and Methods
73.2.1 Generation of Expression Vectors
73.2.2 Western Blotting
73.2.3 TUNEL Assay Detection of Apoptosis
73.2.4 Immunofluorescence
73.2.5 Gene Expression Analysis
73.3 Results
73.3.1 P23H Opsin Protein Has Altered Intracellular Trafficking
73.3.2 Activation of UPR and Autophagy
73.4 Discussion
References
Chapter 74: A Brief Account of Rho GTPases in Retinal Physiology and Pathophysiology
74.1 Introduction
74.2 Rho GTPases in Retinal Development
74.3 Rho GTPases and the Photoreceptor Cytoskeleton
74.4 Rho GTPases in Photoreceptor Degeneration and Survival
74.5 Conclusion
References
Chapter 75: Molecular Clues to Bothnia-Type Retinal Dystrophy
75.1 Introduction
75.2 Materials and Methods
75.2.1 Protein Expression, Purification, and Crystallization
75.2.2 Illumination of 11- cis -Retinal
75.3 Results
75.3.1 The Structure Determination of CRALBP WT and R234W
75.3.2 Photoisomerization of 11- cis -Retinal
75.4 Discussion
References
Chapter 76: A Novel Missense Mutation in Both OPN1LW and OPN1MW Cone Opsin Genes Causes X-Linked Cone Dystrophy (XLCOD5)
76.1 Introduction
76.2 Materials and Methods
76.2.1 Ophthalmic Assessment
76.2.2 Molecular Genetic Analysis
76.2.3 Immunoblotting and Immunocytochemistry
76.3 Results
76.3.1 Phenotype of the XLCOD5 Family
76.3.2 Molecular Genetic Analysis
76.4 Discussion
References
Chapter 77: A Potential Cytosolic Function of Bestrophin-1
77.1 Introduction
77.2 Best's Vitelliforme Macular Dystrophy
77.3 The Function of Bestrophin-1
77.4 The Localization of Bestrophin-1
77.5 Cytoplasmic Function of Bestrophin-1
References
Chapter 78: Modeling the Structural Consequences of BEST1 Missense Mutations
78.1 Introduction
78.2 Materials and Methods
78.2.1 Topology Prediction
78.2.2 Prediction of Protein Structure
78.3 Results
78.3.1 Canine Bestrophin-1 Topology
78.3.2 Comparative Protein Modeling
78.4 Discussion
References
Chapter 79: Microglial Activation and Transcriptomic Changes in the Blue Light-Exposed Mouse Retina
79.1 Introduction
79.2 Materials and Methods
79.2.1 Blue Light Exposure of MacGreen Mice
79.2.2 Retinal Cross Sections and Whole Mounts
79.2.3 RNA Isolation and Reverse Transcription
79.2.4 DNA Microarrays
79.2.5 Quantitative Real-Time PCR
79.3 Results
79.3.1 Microglia Accumulate in Blue Light-Induced Retinal Lesions
79.3.2 Transcriptomic Changes in the Blue Light-Exposed Retina
79.4 Discussion
References
Chapter 80: Overexpression of ROM-1 in the Cone-Dominant Retina
80.1 Introduction
80.2 Materials and Methods
80.2.1 Generation of ROM-1 Transgenic Mice
80.2.2 Gel Electrophoresis and Western Blot Analysis
80.2.3 Electroretinography (ERG)
80.2.4 Electron Microscopy
80.3 Results
80.3.1 Expression of ROM-1 Protein in Transgenic Mice
80.3.2 Overexpression of ROM-1 Exerts Negative Effects on Cone Function and Structure
80.4 Discussion
References
Chapter 81: Analysis of the RPE Sheet in the rd10 Retinal Degeneration Model
81.1 Introduction
81.2 Methods
81.2.1 RPE Flatmount Technique
81.2.2 ZO-1 Staining
81.2.3 Imaging
81.2.4 Statistics
81.3 Results
81.4 Discussion
81.5 Conclusions
References
Chapter 82: Networks Modulating the Retinal Response to Injury: Insights from Microarrays, Expression Genetics, and Bioinformatics
82.1 Introduction
82.2 Gene Expression After Retinal Injury
82.3 Expression Genetics of Retinal Injury Genes
82.4 Bioinformatics Can Predict Candidate Modulators
82.5 Predicted Networks Require Validation
82.6 Conclusion
References
Chapter 83: Mislocalization of Oligomerization-Incompetent RDS is Associated with Mislocalization of Cone Opsins and Cone Transducin
83.1 Introduction
83.2 Materials and Methods
83.2.1 Construction of the Transgene
83.2.2 Antibodies and Immunohistochemistry
83.3 Results
83.3.1 OS Proteins are Normally Localized in COP-T/nrl - / -
83.3.2 GNAT2 is Mislocalized in COP-T/WT
83.4 Discussion
References
Chapter 84: HSP70 Gene Expression in the Zebrafish Retina After Optic Nerve Injury: A Comparative Study Under Heat Shock Stresses
84.1 Introduction
84.2 Materials and Methods
84.2.1 Animals and Treatment
84.2.2 RNA Isolation and RT-PCR
84.2.3 Tissue Preparation
84.2.4 Immunohistochemistry
84.2.5 In Situ Hybridization
84.3 Results
84.3.1 The Expression of HSP70 and HSF-1 in the Zebrafish Retina After ONI
84.3.2 The Expression of HSP70 and HSF-1 in the Zebrafish Retina After Heat Shock
84.4 Discussion
References
Part IX: Retinal Development, Physiology, Cell and Molecular Biology
Chapter 85: Restoration of Retinal Development in Vsx2 Deficient Mice by Reduction of Gdf11 Levels
85.1 Introduction
85.2 Materials and Methods
85.2.1 Animals
85.2.2 Histology and In Situ Hybridization
85.3 Results
85.4 Discussion
References
Chapter 86: The Different Functions of Norrin
86.1 Introduction
86.2 Norrie Disease
86.3 Norrin
86.4 Angiogenic Properties of Norrin
86.5 Neuroprotective Properties of Norrin
86.6 The Role of Norrin in Reproduction and Development
References
Chapter 87: Roles of Homeobox Genes in Retinal Ganglion Cell Differentiation and Axonal Guidance
87.1 Introduction
87.2 Brn-3 Genes
87.3 Dlx Genes
87.4 Vax Genes
87.5 Islet Genes
87.6 Summary
References
Chapter 88: Unraveling the Molecular Mystery of Retinal Pigment Epithelium Phagocytosis
88.1 Introduction
88.2 Materials and Methods
88.2.1 Open Reading Frame Phage Display
88.2.2 RPE Phagocytosis Assay
88.2.3 MerTK Ligand Studies
88.3 Results
88.3.1 Unbiased Identification of Tulp1 as a Phagocytosis Ligand
88.3.2 Characterization of MerTK as a Tulp1 Receptor
88.4 Discussion
References
Chapter 89: Isolating Photoreceptor Compartment-Specific Protein Complexes for Subsequent Proteomic Analysis
89.1 Introduction
89.2 Materials and Methods
89.2.1 Animals
89.2.2 Time-Controlled Transcardiac Perfusion Crosslinking (tcTPC)
89.2.3 Preparation of Retinal Sections
89.2.4 Laser Microdissection
89.2.5 Retinal Homogenate
89.2.6 Western Blotting Analysis
89.3 Results
89.3.1 Isolation and Capture of Photoreceptor Compartments
89.3.2 Tulp1 Complexes in the Retina
89.3.3 Tulp1 Compartment-Specific Complexes
89.4 Discussion
References
Chapter 90: Expression of the Integrin Coreceptor Transglutaminase-2 in the RPE In Vivo and in Culture
90.1 Introduction
90.2 Materials and Methods
90.2.1 Animals and Tissue Collection
90.2.2 Immunofluorescence Microscopy
90.2.3 Immunoblotting
90.3 Results
90.3.1 Comparison of TG2 Protein Levels of Wild-Type and ®5 -/- Mouse Eyecups
90.3.2 Localization of TG2 in Wild-Type Mouse Retina
90.3.3 Localization of TG2 in Wild-Type Rat RPE in Primary Culture
90.4 Discussion
References
Chapter 91: On Your Marks. Get Bound. Internalize!
91.1 Introduction
91.2 On Your Marks.
91.3 Get Bound.
91.4 Internalize
91.5 Perspectives
References
Chapter 92: Endo-Lysosome Function in the Retinal Pigment Epithelium in Health and Disease
92.1 Introduction
92.2 Late Endosomes and Lysosomes: Function and Dysfunction
92.3 Late Endosomes and Lysosomes in the RPE
92.4 RPE Late Endosome-Lysosome Dysfunction, Impaired Cholesterol Trafficking, and Retinal Degenerations
92.5 Conclusions
References
Chapter 93: a v b 5 Integrin-Dependent Diurnal Phagocytosis of Shed Photoreceptor Outer Segments by RPE Cells Is Independent of the Integrin Coreceptor Transglutaminase-2
93.1 Introduction
93.2 Materials and Methods
93.2.1 Animals and Tissue Collection
93.2.2 Histology
93.2.3 Quantification of POS Phagosomes in the RPE
93.3 Results
93.3.1 TG2 -/- Mice Display Normal Retinal Architecture
93.3.2 The RPE in TG2 -/- Mice Displays a Normal Diurnal Peak of Rod POS Phagocytosis
93.4 Discussion
References
Chapter 94: Trafficking of Presynaptic PMCA Signaling Complexes in Mouse Photoreceptors Requires Cav1.4 a 1 Subunits
94.1 Introduction
94.2 Materials and Methods
94.2.1 Animals
94.2.2 Immunohistochemistry
94.3 Results
94.3.1 Nob2 Mutation of Cav1.4 Is Associated with Mislocalization of PMCA1 but not PMCA2
94.4 Discussion
References
Chapter 95: Roles for AMP-Activated Protein Kinase in RPE Cell Function
95.1 Introduction
95.2 Mechanistic Regulation of AMPK Activity
95.2.1 Allosterical Activation of AMPK
95.2.2 Activation of AMPK via Thr 172 Pphosphorylation by AMPK Kinase
95.2.3 AMPK Inactivation
95.3 AMPK and RPE Cell Barrier Function
95.4 AMPK and RPE Cell Phagocytosis
95.5 AMPK and RPE Cell Inflammatory Responses
95.6 AMPK and RPE Cell Survival
95.7 Perspectives
References
Chapter 96: Genome-Wide Occupancy Analysis by ChIP-chip and ChIP-Seq
96.1 Introduction
96.2 ChIP-chip and ChIP-Seq by Illumina and ABI/SOLiD
96.3 Insights from Genome-Wide Occupancy Studies
96.3.1 Location of Transcription Factor Occupancy
96.3.2 Chromatin Signatures
96.4 Applications of ChIP-chip and ChIP-Seq to the Study of Photoreceptor
96.5 Conclusions and Perspectives
References
Chapter 97: The Bisretinoids of RPE Lipofuscin: A Complex Mixture
97.1 RPE Lipofuscin Is Unique in Its Origin
97.2 A2E, Isomers, and Precursors
97.3 The All- Trans -Retinal Dimer Series of Lipofuscin Fluorophores
97.4 The Bisretinoid A2-DHP-PE
97.5 Photooxidized Forms of Bisretinoid Pigments in RPE Lipofuscin
97.6 Discussion
References
Chapter 98: Biochemical Characterization of Cone Cyclic Nucleotide-Gated (CNG) Channel Using the Infrared Fluorescence Detection System
98.1 Introduction
98.2 Materials and Methods
98.2.1 Infrared Fluorescence Western Detection of Cone CNG Channel
98.2.2 Chemical Cross-Linking
98.2.3 Blue Native-PAGE
98.3 Results
98.3.1 Simultaneous Detection of CNGA3 and CNGB3 in the Mouse Retina by Infrared Fluorescence Western Detection
98.3.2 Analysis of Cone CNG Channel Complexes Using Chemical Cross-Linking and Infrared Fluorescence Detection
98.3.3 Analysis of Cone CNG Channel by Blue Native-PAGE
98.4 Discussion
References
Chapter 99: Ras-Associating Domain Proteins: A New Class of Cyclic Nucleotide-Gated Channel Modulators
99.1 Introduction
99.2 Materials and Methods
99.2.1 Cell Culture Studies and Vectors
99.2.2 Sequence Alignment and Domain Assessment
99.2.3 Statistical Methods
99.3 Results
99.3.1 Assessment of RA Domains in PHLPP1 and PHLPP2
99.3.2 PHLPP1 and 2 Do Not Have Channel Modulatory Properties
99.4 Discussion
References
Chapter 100: Tulp1 Is Involved in Specific Photoreceptor Protein Transport Pathways
100.1 Introduction
100.2 Materials and Methods
100.2.1 Animals
100.2.2 Immunofluorescent Staining of Retinal Sections
100.3 Results
100.4 Discussion
References
Chapter 101: Potential Cellular Functions of N -Ethylmaleimide Sensitive Factor in the Photoreceptor
101.1 Introduction
101.2 NSF in Photoreceptor Synaptic Regulation
101.3 NSF in Photoreceptor Membrane Protein Trafficking
101.4 Summary
References
Chapter 102: Identification of Pigment Epithelium-Derived Factor Receptor (PEDF-R) Antibody Epitopes
102.1 Introduction
102.2 Materials and Methods
102.2.1 Peptides, Proteins, and Antibodies
102.2.2 Slot Blot
102.2.3 Membrane Fractionation
102.2.4 Polyacrylamide Gel Electrophoresis
102.2.5 Immuno-Blot
102.3 Results
102.3.1 Immunoreactivity to Recombinant PEDF-R Polypeptide Fragments
102.3.2 Immunoreactivity to Synthetic PEDF-R Peptides
102.3.3 Immunoreactivity to Native Rat PEDF-R
102.4 Discussion
References
Chapter 103: HCN1 Channels Significantly Shape Retinal Photoresponses
103.1 Introduction
103.2 Mechanism of HCN1 Channel Activity in Normal Photoreceptor
103.3 Altered Single-Flash ERG Responses in HCN1 -/- Mice
103.4 Reduction in Scotopic ERG Flicker Fusion Frequency in HCN1 -/- Mice
103.5 Summary and Perspective
References
Chapter 104: The Role of the P2X7 Receptor in the Retina: Cell Signalling and Dysfunction
104.1 Introduction
104.1.1 ATP and Purinergic Receptors
104.1.2 ATP Storage, Release and Degradation
104.1.3 Purine Receptors
104.2 The P2X7 Receptor
104.2.1 Role of the P2X7 Receptor in Neuronal Modulation in the Retina
104.2.2 Role of the P2X7 Receptor in Neuronal Degeneration in the Retina
104.2.3 Role of the P2X7 Receptor in Müller Cells
104.2.4 Role of the P2X7 Receptor in Retinal Microglial Cells
104.3 Conclusion
References
Chapter 105: A Tale of Two Kinases in Rods and Cones
105.1 Introduction
105.2 The Function of GRK7
105.3 Regulation of GRK1 and GRK7 Activity Under Changing Light Conditions
References
Chapter 106: Protein Tyrosine Phosphatase 1B: A Novel Molecular Target for Retinal Degenerative Diseases
106.1 Introduction
106.2 Importance of Insulin Receptor Signaling in Retina
106.3 Interaction Between PTP1B and IR
106.4 Implication of PTP1B Activity in Retinal Diseases
106.5 PTP1B as a Therapeutic Target
106.6 Conclusions
References
Chapter 107: Protein Tyrosine- O -Sulfation in Bovine Ocular Tissues
107.1 Introduction
107.2 Materials and Methods
107.2.1 Isolation of Tissues from Bovine Eyes
107.2.2 Western Blot of Tissue Lysates
107.3 Results
107.4 Discussion
References
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