Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Офтальмология / Английские материалы / Studies on Retinal and Choroidal Disorders_Stratton, Hauswirth, Gardner_2012.pdf
X
- •Preface
- •Contents
- •Contributors
- •1.1 Introduction
- •1.2 Pathogenesis of AMD
- •1.2.1 Oxidative Damage
- •1.2.2 Lipofuscin Accumulation
- •1.2.4 Complement Mutations
- •1.2.5 Mitochondrial Damage
- •1.2.6 DICER 1
- •1.3 Treatment
- •1.3.1 Antioxidants
- •1.3.2 Visual Cycle Modulators
- •1.3.4 Neurotrophic Agents
- •1.3.5 Antiangiogenic Agents
- •1.3.5.1 Intracellular Angiogenic Factor Production
- •1.3.5.2 Extracellular Angiogenic Factors
- •1.3.6 Endothelial Cell Receptor Binding
- •1.3.7 Endothelial Cell Activation
- •1.3.8 Endothelial Cell Proliferation
- •1.3.9 Endothelial Cell Directional Migration
- •1.3.10 Extracellular Matrix Remodeling
- •1.3.11 Tube Formation
- •1.3.11.1 Loop Formation (Arteriovenous Differentiation)
- •1.3.11.2 Vascular Stabilization
- •1.4 Combination Therapy
- •1.5 Conclusions
- •References
- •2.1 Introduction
- •2.1.1 Complement Pathways
- •2.1.2 Oxidative Stress
- •2.3.1 The Mouse CNV Model
- •2.3.2 RPE Monolayers
- •2.3.3 Concept
- •2.5 Summary and Outlook
- •References
- •3.1 Introduction
- •3.2.1 Advanced Glycation End Products
- •3.2.2 Carboxyethylpyrrole
- •3.2.3 Oxidation Products of Lipofuscin
- •3.3 Summary and Conclusions
- •References
- •4.1 Introduction
- •4.2 Oxidative Stress and AMD
- •4.2.1 Basic Concepts on Oxidative Stress
- •4.2.2 Oxidative Stress in AMD
- •4.3 Malondialdehyde in AMD
- •4.3.1 Lipid Peroxidation and Malondialdehyde
- •4.3.2 Materials and Methods
- •4.3.2.1 RPE Cell Culture
- •4.3.2.2 Patients
- •4.3.2.3 MDA Assay
- •4.3.3 MDA Levels in Cultured RPE Cells and in Patients with AMD
- •4.4 Summary and Conclusions
- •References
- •5.1 Introduction
- •5.2 The Origin and Housing of RPE Lipofuscin
- •5.3 Bisretinoid Constituents of RPE Lipofuscin
- •5.3.1 A2E, Isomers and Precursors
- •5.3.4 Photooxidized Forms of Bisretinoid Pigments
- •5.4 Photoreactivity of RPE Lipofuscin
- •5.5 Photooxidation of RPE Bisretinoids
- •5.6 Bisretinoid Photodegradation
- •5.7 Potential for Cell and Tissue Damage
- •5.9 A Role for Antioxidants
- •5.10 Conclusions
- •References
- •6.1 Introduction
- •6.1.1 RPE Lipofuscin Accumulation with Age and Relation to AMD
- •6.1.2 Known Chromophores Found in RPE Lipofuscin and the Mechanism of Damage
- •6.1.3 Formation of Higher Molecular Weight Material
- •6.1.4 Current Studies and Possible Structures of Higher Molecular Weight Products
- •6.1.4.1 Lipofuscin Extracts
- •6.1.4.3 Esters and Aldehydes
- •6.2 Conclusions
- •References
- •7.2 DHA in Photoreceptor Cells
- •7.3 Neuroprotectin D1 Synthesis is an Early Response to Oxidative Stress in RPE Cells
- •7.5 Neurotrophins Trigger the Synthesis and Polarized Secretion of Neuroprotectin D1 from Human RPE Cells
- •7.6 Photoreceptor Outer Segment Phagocytosis Induces RPE Cell Survival Signaling with Associated Synthesis of NPD1 During Oxidative Stress
- •References
- •8.1 Introduction
- •8.2.1 Subcellular Localization
- •8.2.2 Expression Levels in the Retina
- •8.4.3 Regulation of RDH12 Expression and Activity During Chronic and Acute Stress
- •8.5 RDH12 and Leber Congenital Amaurosis
- •8.5.1 Inactivating Mutations of RDH12
- •8.5.2 Loss of Which RDH12 Function Induces LCA?
- •8.6 Summary and Conclusions
- •References
- •9.1 Introduction
- •9.2 GSH Metabolism: General Principles
- •9.2.2 Role of Mitochondrial GSH in Protection
- •9.2.3 GSH as a ROS Scavenger
- •9.2.4 GSH Distribution in the Retina and RPE in Health and Disease
- •9.5 Future Perspectives
- •References
- •10.1 Introduction
- •10.2 Mitochondria
- •10.2.1 Mitochondrial Biogenesis and Maintenance
- •10.2.2 Mitochondrial Removal and Degradation
- •10.3 Mitochondria and Reactive Oxygen Species
- •10.3.1 Reactive Oxygen and Nitrogen Species (ROS and RNS)
- •10.3.2 Mitochondria are a Major Source of Intracellular ROS
- •10.3.3 Other Sources of ROS in the Retina
- •10.4 The Mitochondrial Genome
- •10.4.1 Susceptibility of Mitochondrial DNA to Oxidative Stress
- •10.4.2 Mitochondrial DNA Damage
- •10.4.3 Mitochondrial DNA Repair Pathways
- •10.4.4 The Mitochondrial Base Excision Repair (mtBER) Pathway
- •10.4.6 Other Mitochondrial DNA Repair Pathways
- •10.4.6.2 Mismatch Repair (MMR)
- •10.4.6.3 Translesion Synthesis (TLS) and Damage Tolerance
- •10.4.6.4 Nucleotide Excision Repair (NER)
- •10.4.7 Intramitochondrial Localization of DNA Repair Proteins
- •10.4.8 mtDNA Damage Sensing and Signaling
- •10.4.9 Import of Nuclear Encoded DNA Repair Enzymes into the Mitochondria
- •10.5 Mitochondrial DNA Damage/Repair in the Retina and RPE
- •10.5.1 Mitochondrial DNA Damage/Repair in the RPE
- •10.5.2 DNA Repair and the Adaptive Response in the RPE
- •10.6 Pathologies Associated with Mitochondrial Dysfunction and Oxidative Stress in the Retina
- •10.6.2 Diabetic Retinopathy
- •10.6.3 Glaucoma
- •10.6.4 Uveitis
- •10.7 Pathologies Associated with Inherited Mitochondrial Disorders
- •10.8 Potential Therapeutic Options for Targeting Mitochondrial DNA Damage
- •10.8.1 Mitochondrial Biogenesis
- •10.8.2 Enhancing mtDNA Repair
- •10.8.3 Antioxidants
- •10.8.4 Autophagy
- •10.9 Conclusion
- •References
- •11.1 Introduction
- •11.2 ER Function in Normal Physiology
- •11.2.1 Major Roles of Rough ER (RER) and Smooth ER (SER)
- •11.2.2 ER and Oxidative Protein Folding
- •11.2.3 ER Resident Proteins
- •11.2.4 Potential Threat to ER Function in RPE
- •11.3 ER Response to Oxidative Stress in RPE
- •11.3.2 Initiation of UPR to Alleviate ER Burden
- •11.4 Chronic ER Stress and Oxidative Stress in the Vicious Cycle of Apoptosis Induction
- •11.5 Future Perspectives
- •References
- •12.1 Introduction
- •12.2 Iron Homeostasis
- •12.2.1 General Iron Homeostasis
- •12.2.2 Iron Import into the Retina
- •12.2.2.1 Transferrin Mediated Transport
- •12.2.2.3 Dexras
- •12.2.3 Iron Storage
- •12.2.3.1 Ferritin
- •12.2.3.2 Mitochondrial Ferritin
- •12.2.4 Iron Export
- •12.2.4.1 Ceruloplasmin
- •12.2.4.2 Hephaestin
- •12.2.4.3 Ferroportin and Hepcidin
- •12.3 Disruption of Iron Homeostasis and Oxidative Damage
- •12.4 Retinal Disorders Resulting from Abnormal Retinal Iron Metabolism
- •12.4.2 Aceruloplasminemia
- •12.4.3 Hemochromatosis
- •12.4.4 Friedreich’s Ataxia
- •12.4.6 Siderosis
- •12.4.7 Subretinal Hemorrhage
- •12.5 Potential Therapeutics
- •References
- •13.1 Vascular Endothelial Growth Factor and Its Functions in the Retina
- •13.1.1 VEGF Isoforms
- •13.1.2 VEGF Functions
- •13.1.3 Cells Secreting VEGF in the Retina
- •13.1.3.1 Retinal Pigment Epithelium
- •13.1.3.2 Müller Cells
- •13.1.3.3 Astrocytes
- •13.1.3.4 Pericytes
- •13.1.4 VEGF Receptors and VEGF Induced Signal Transduction
- •13.1.4.1 VEGF Receptors
- •VEGFR-1
- •VEGFR-2
- •Neuropilin
- •Heparan Sulfate Proteoglycan
- •13.2 Regulation of VEGF Expression
- •13.2.1 Transcriptional Regulation
- •13.2.2 Translational Regulation
- •13.2.3 Hypoxia Induced VEGF Regulation
- •13.2.4 Posttranslational Regulation
- •13.2.5 Autocrine VEGF Regulation
- •13.2.6 Pathological VEGF Production
- •13.2.6.1 Hyperglycemia
- •13.2.6.2 Oxidative Stress
- •13.2.6.3 Cytokines
- •13.2.6.4 Endoplasmic Reticulum
- •13.2.6.5 Additional Factors
- •13.3.1 Pegaptanib
- •13.3.2 Bevacizumab and Ranibizumab
- •13.3.4 siRNA
- •13.3.5 Small Molecule Tryrosine Kinase Inhibitors
- •13.3.6 Other Inhibitors
- •13.4.2 Interaction of VEGF Antagonists with Antiangiogenic VEGFxxxb
- •13.5 Conclusion
- •References
- •14.1 Introduction
- •14.2 NADPH Oxidase and Redox Signaling
- •14.3 Expression of NADPH Oxidase Subunit p22phox in the Retina
- •14.4 NADPH Oxidase and Choroidal Neovascularization
- •14.5 Implication and Therapeutic Potential of NADPH Oxidase in Development of CNV
- •14.6 Summary and Future Perspective
- •References
- •15.1 Introduction
- •15.2 Aging
- •15.3 Deposition and Formation of Oxidized LDL
- •15.6 Treatments for AMD
- •15.7 Conclusions
- •References
- •16.1 Introduction
- •16.2 HGF and Its Receptor (MET)
- •16.2.1 Production and Secretion of HGF
- •16.2.2 MET and Biological Effects of HGF
- •16.2.3 Signaling Pathways of HGF
- •16.2.4 HGF and MET in Disease States
- •16.4 HGF Protects RPE Cells from Oxidative Stress
- •16.4.1 HGF and RPE Cells
- •16.4.2 HGF Promotes Cell Survival
- •16.4.3 HGF Protects Cells from Oxidative Stress
- •16.4.4 HGF Protects RPE Cells from Hydrogen Peroxide
- •16.4.5 HGF Protects RPE Cells Against Ceramide Damage
- •16.4.6 HGF Protects RPE Cells from Glutathione Depletion
- •References
- •17.1 Introduction
- •17.2.1 Fundoscopy
- •17.2.2 Histology
- •17.2.3 Ultrastructure
- •17.3.1 Lipofuscin (A2E)
- •17.3.3 HtrA2/Omi
- •References
- •18.1 Introduction
- •18.2 Systemic Markers of Oxidative Stress
- •18.2.1 Redox Status
- •18.2.2 DNA Damage
- •18.2.4 Lipid Peroxidation
- •18.3 Defenses Against Oxidative Stress
- •18.3.1 Antioxidants
- •18.3.2 Antioxidant Enzymes
- •18.4 Oxidative Stress and Genetics
- •18.4.1 Antioxidant Enzyme Polymorphisms
- •18.5 Environmental Exposures and Oxidative Stress
- •18.5.1 Smoking
- •18.5.2 Light Exposure
- •18.6 AMD Treatments and Oxidative Stress
- •18.8 Summary and Conclusions
- •References
- •19.1 Characteristics of Cerium Oxide Nanoparticles
- •19.3 Mechanism of Nanoceria Uptake, Internalization, and Localization in the Cell
- •19.4 Biological Effect, Functional Mechanism, and Applications
- •19.4.1 Bacteria
- •19.4.2 Plants
- •19.4.3 Medical Usage
- •19.4.3.1 Radioprotectants
- •19.4.3.2 Burn Treatment
- •19.4.4 Medical Imaging
- •19.5 Stability of Nanoceria Under storage Conditions and Its Longevity in the Cell In Vivo
- •19.6 Oxidative Damage Results in Neurodegeneration
- •19.7.1 Prolong Cellular Life Span
- •19.7.2 Cardioprotection
- •19.8 Treatment of Ocular Disorders
- •19.8.1 Methodology
- •19.8.2 Prevention of Light Damage and Rescue of Retinal Function
- •19.8.3 Treatment of Degenerative Ocular Diseases
- •19.8.4 Treatment of Ocular Neovascular Diseases
- •19.9 Toxicity and Environmental Impacts
- •19.10 Conclusion and Future Directions
- •References
- •20.1 Introduction
- •20.2 Retinal Progenitor Cells (RPCs) Are Multipotential
- •20.4 Therapeutic Strategies for Repair and Regeneration of Retinal Cells: Repair of the RPE
- •20.5 Challenges for RPE Stem Cell Therapy
- •20.6 Characterization of RPE-Like Cells Derived from BMDCs
- •20.7 BMDCs Differentiate into Retinal Cells
- •20.8 Summary and Future of Cell Therapy for Dysfunctional RPE
- •References
- •21.1 Introduction
- •21.2 Carotenoids in Retinal Diseases
- •21.4 Polyphenols or Phenolic Esters in Retinopathies
- •21.4.1 Caffeic Acid Phenethyl Ester
- •21.4.2 Catechin
- •21.4.3 Curcumin
- •21.4.4 Proanthocyanidin
- •21.4.5 Resveratrol
- •21.5.2 Sulforaphane
- •21.6 Vitamins in Retinopathies
- •21.6.1 Vitamin A
- •21.7 Perspectives
- •References
- •22.1 Introduction
- •22.1.1 Neuroprotection as a Strategy for Retinal Degenerative Disease
- •22.2.2 Putative Mechanisms of CNS Neuroprotection
- •22.3.9 Conclusion
- •22.4 Mechanisms of Retinal Protection
- •22.4.1 Insights from In Vitro Models
- •22.5.1 Background to the Disease and the Associated Preclinical Data
- •22.5.2 Overview of the Clinical Development Program
- •References
- •23.1 Introduction
- •23.2 Pathogenesis
- •23.4 Pegaptanib
- •23.5 Bevacizumab
- •23.6 Ranibizumab
- •23.7.1 Ranibizumab
- •23.7.2 Bevacizumab
- •23.8 Comparison of AMD Treatment Trials (CATT)
- •23.9 Management of Nonresponders
- •23.11 Conclusion
- •References
- •24.1 Introduction
- •24.2 Rationale for Combination Therapy
- •24.3 Supporting Evidence for Combination Therapy
- •24.4 Currently Applied Combination Therapies
- •24.5 Challenges for Combination Therapy
- •References
- •25.1 Human Endothelial Progenitor Cells
- •25.3 Function of EPCs
- •25.3.1 EPCs in Vascular Repair and Neovascularization
- •25.4 EPCs in Diabetes
- •25.4.1 EPC as a Biomarker in Diabetes
- •25.4.1.1 EPC Dysfunction in Diabetes
- •25.4.1.2 Oxidative Stress and EPC Dysfunction in Diabetes
- •25.4.1.3 Therapeutic Angiogenesis by EPCs in Diabetic Retinopathy
- •25.5 Conclusion
- •References
- •26.1 Introduction
- •26.1.1 Nitric Oxide
- •26.1.2 Nitric Oxide Regulation
- •26.1.3 Nitric Oxide in Normal and Pathophysiological Conditions
- •26.2 Retinal Vascular Diseases: The Role of iNOS
- •26.2.1 Nitric Oxide in Diabetic Retinopathy
- •26.2.2 iNOS in Diabetic Retinopathy
- •26.2.2.2 iNOS and Leukocyte Adhesion to Retinal Vessels
- •26.2.2.3 iNOS and Retinal Cell Death
- •26.2.3 Proliferative Retinal Diseases
- •26.2.3.1 iNOS and Proliferative Retinal Diseases
- •26.2.3.2 iNOS and Ocular Neovascularization in Retinal Vascular Diseases
- •26.3 Conclusions
- •References
- •27.1 Introduction
- •27.2 Animal Model
- •27.2.1 LHP Preparation and Injection Procedure
- •27.2.2 Acridine Orange Digital Fluorography
- •27.3 Experimental Results
- •27.3.1 Leukocyte Rolling
- •27.3.2 Accumulated Leukocytes in the Retinal Microcirculation
- •27.3.3 Diameter of Major Retinal Vessels
- •27.3.4 SOD Treatment
- •27.4 Discussion
- •27.5 Conclusions
- •References
- •28.1 Introduction
- •28.1.2 Metabolism and Balance in Generation and Quenching of ROS
- •28.2 Role of Oxygen Concentration on Generation of ROS in the Developing Retina
- •28.3.1 Perinatal Considerations
- •28.3.2 Neonatal Considerations
- •28.3.2.1 Polyunsaturated Fatty Acids in Retina and Brain
- •28.3.2.2 Increased Oxidation
- •28.3.2.3 Reduced Antioxidant Enzyme Systems
- •28.3.3 Environmental Stimuli
- •28.3.3.1 Light
- •28.3.3.2 Oxygen Changes in Development and Prematurity
- •28.3.3.3 Nutrition
- •28.3.3.4 Effect of Blood Transfusions on Oxidative Stress in Prematurity
- •28.4 Evidence from Animal Models
- •28.4.1 Background
- •28.4.2 Effects of Hypoxia on Bioenergetic Oxygen Sensor Mechanisms and Related to ROP
- •28.4.2.2 NADPH Oxidase
- •28.4.2.3 Cytochrome p450 Monooxygenases (CYP)
- •28.4.2.4 eNOS
- •28.4.2.5 Heme Oxygenase
- •28.4.2.6 Metabolic Effects of Hypoxia
- •28.4.3 Laboratory Evidence of Antioxidants on Animal Models of ROP
- •28.5 Clinical Studies of Antioxidants on ROP
- •28.6 Genetics
- •28.7 Summary
- •References
- •29.1 Introduction
- •29.1.1 Oxidative Stress in Glaucoma
- •29.1.2 Oxidative Stress in Diabetic Retinopathy
- •29.1.3 Oxidative Stress in Age Related Macular Degeneration
- •29.1.4 Vascular Endothelial Growth Factor
- •29.1.5 VEGF Mediated Neuroprotection
- •29.1.6 Mechanisms of VEGF Protection Against Oxidative Stress
- •References
- •30.1 Introduction
- •30.1.1 Oxidation and Oxidative Stress
- •30.1.2 Reactive Oxygen Intermediates
- •30.1.3 ROIs and Cellular Retinal Damage
- •30.1.4 Light, Cellular Retinal Damage and AMD
- •30.1.5 Carotenoids
- •30.1.6 Chemistry of Carotenoids: Basic Structural Components
- •30.2 Building Blocks
- •30.3 The Polyene Backbone
- •30.5 Terminal Groups
- •30.5.1 Source of Macular Carotenoids
- •30.5.2 Macular Carotenoids: The Origins of Macular Pigment
- •30.5.3 The Functions of the Macular Carotenoids as Macular Pigment for AMD
- •30.6 Antioxidant Properties
- •30.6.1 The Functions of the Macular Carotenoids as Macular Pigment for Visual Performance
- •References
- •31.1 Introduction
- •31.2 Composition and Distribution
- •31.3 Selective Uptake and Deposition Process of MP
- •31.4 Measurements
- •31.4.1 Heterochromatic Flicker Photometry
- •31.4.4 Resonance Raman Spectroscopy
- •31.5 Antioxidant Mechanism of MP and Its Relation to Retinal Health and Disease
- •31.5.1 Oxidative Stress in Human Retina and the Antioxidant Mechanism of MP
- •31.5.2 MP in Human Eye Health and Disease
- •31.5.2.2 MacTel
- •31.5.2.3 Acuity
- •31.6 Ocular Carotenoid Supplementation Studies
- •31.7 Conclusion
- •References
- •Index
- •About the Authors
4 Role of Malondialdehyde in the Age-Related Macular Degeneration |
89 |
Fig. 4.1 Human RPE cell treated by t-butylhydroperoxide (t-BuOOH) 6 h
Fig. 4.2 Human RPE cell treated with t-BuooH 6 h
4.3.3MDA Levels in Cultured RPE Cells and in Patients with AMD
MDA levels in RPE cells treated with t-BuOOH were Þve times higher than RPE cells without treatment (StudentÕs t test, P < 0.001) (Fig. 4.1). Such elevation was dose and time-dependent (Figs. 4.2 and 4.3). The maximal elevation of MDA level was observed in samples treated with 600 mM t-BuooH for 6 h. Plasma levels of MDA in patients with AMD were signiÞcantly higher (mean = 0.782, n = 53) compared with their age matched controls (mean = 0.572, n = 37) (StudentÕs t test, P < 0.05) (Fig. 4.4).
Соседние файлы в папке Английские материалы