- •Drug Product Development for the Back of the Eye
- •Preface
- •Contents
- •Contributors
- •1.1 Introduction
- •1.2 A Strategic Overview of Drug Delivery Systems
- •1.3 Specific Approaches to Drug Delivery for the Posterior Segment
- •1.3.1 The Influence of Physicochemical Properties on Drug Delivery and Pharmacokinetics
- •1.3.2 The Chosen Route of Administration
- •1.3.3 Location of the Target Tissue
- •1.3.4 Potency of the Drug
- •1.3.5 Need for Continuous or Pulsatile Delivery
- •1.3.6 Duration of Drug Delivery Necessary to Induce and Maintain Efficacy
- •1.3.7 Type of Drug Delivery System Selected
- •1.3.8 Pharmacokinetic (PK) Properties of the Drug
- •1.3.9 Local and Systemic Toxicity of the Drug and its Metabolites
- •1.3.10 Previous Ocular Use of Excipients
- •1.3.11 Development and Strategic Team Input
- •References
- •2.1 Introduction
- •2.2 Posterior Segment as a Sampling Site
- •2.3 Principle of Microdialysis
- •2.3.1 Extraction Efficiency/Recovery
- •2.4.1 Anesthetized Animal Models
- •2.4.2 Conscious Animal Model
- •2.5 Vitreal Pharmacokinetics in Animals Other than Rabbits
- •2.6 Summary
- •References
- •3.1 Commercial Fluorophotometer
- •3.2 Normal Human Subject and Rabbit Ocular Fluorescence
- •3.3 Fluorophotometry Applications
- •3.3.1 Tear Turnover Rate (%/min)
- •3.3.2 Corneal Epithelial Cell Layer Permeability Methodologies
- •3.3.3 Eye Bath Technique
- •3.3.4 Single Drop Technique to Measure Epithelial Permeability
- •3.3.5 Eye Bath Technique to Measure Epithelial Permeability
- •3.4 Clinical Applications of Fluorophotometry
- •3.5.1 Transscleral Pathways
- •3.5.2 Suprachoroidal Injection
- •3.6 Retrobulbar Fluorescein Injection
- •3.7 Intravenous Fluorescein Injection In Vivo
- •3.8 Ocular Uptake of Fluorescein from Topical Eye Drops
- •References
- •4.1 Introduction
- •4.1.1 Role of the Blood-Retinal Barrier as a Dynamic Interface
- •4.1.2 Potential Approach of Blood-Retinal Barrier-Targeted Systemic Drug Delivery to the Retina
- •4.2.1 Amino Acid-Mimetic Drugs
- •4.2.2 Monocarboxylic Drugs
- •4.2.3 Nucleoside Analogs
- •4.2.4 Folate Analogs
- •4.2.5 Organic Cationic Drugs
- •4.2.6 Opioid Peptides and Peptidomimetic Drugs
- •4.2.7 Antioxidants
- •4.2.7.1 Vitamin C
- •4.2.7.2 Vitamin E
- •4.2.7.3 Cystine
- •4.2.8 Miscellaneous Protective Compounds
- •4.2.8.1 Creatine
- •4.2.8.2 Taurine
- •4.3.1 Organic Anion Transporter 3 (OAT3, SLC22A8)
- •4.3.3 P-Glycoprotein (ABCB1)
- •4.3.4 Multidrug Resistance-Associated Proteins (ABCCs)
- •4.3.6 ABCAs
- •4.4 Conclusions and Perspectives
- •References
- •5.1 Introduction
- •5.2 Drug Distribution
- •5.2.1 Drug Distribution from the Anterior Ocular Surface to the Posterior Segment
- •5.2.2 Studies of Trans-Corneal and Periocular Drug Delivery to the Retina
- •5.2.2.1 The Uvea-Scleral Route
- •5.3 Eye Drops for Posterior Segment Diseases in the Clinic
- •5.4 Summary
- •References
- •6.1 Introduction
- •6.2 Vitreous Anatomy
- •6.2.1 The Inner Limiting Membrane
- •6.3 The Vitreous As a Drug Reservoir
- •6.4 Flow Processes in the Vitreous
- •6.4.1 Flow Patterns
- •6.4.2 Injection and Hydrostatic Effects
- •6.4.3 Diffusion
- •6.4.4 Convective Flow
- •6.5 Clearance Pathways from the Vitreous Compartment
- •6.5.1 Charge and Collagen Interaction
- •6.5.2 Aqueous Clearance
- •6.5.3 Retinal Clearance
- •6.6 Transfer Through the Vitreoretinal Border
- •6.6.1 The Role of the Blood–Retinal Barrier
- •6.6.1.1 Amino Acid Transport
- •6.6.1.2 P-Glycoprotein
- •6.6.1.3 Organic Cationic Transporters
- •6.6.1.4 Organic Anion Transporters
- •6.6.1.5 Other Transporters
- •6.7 The Ageing Vitreous
- •6.7.1 Underlying Mechanisms of Vitreous Degeneration
- •6.7.2 Physical Changes Involved in the Ageing Vitreous
- •6.7.2.1 Pre-Clinical Model of Ageing Vitreous
- •6.7.2.2 Effects of Vitreous Liquefaction on Intravitreal Drug Delivery
- •6.7.3 Vitrectomised Eyes
- •6.7.3.1 Intravitreal Drug Distribution and Clearance in Silicone Oil
- •6.7.4 Role of Ocular Movements in Disordered Vitreous
- •6.8 Concluding Remarks
- •References
- •7.1 Introduction
- •7.2 Drug Delivery to Posterior Segment Ocular Tissues
- •7.3 Scleral Structure and Drug Delivery
- •7.4 Scleral Permeability: Initial Studies
- •7.5 Sustained-Release Delivery In Vitro
- •7.6 In Vivo Studies
- •7.7 Conclusions and Future Directions
- •References
- •8.1 Introduction
- •8.2 Background
- •8.3 Posterior Segment Delivery
- •8.4 Transscleral and Intrascleral Drug Delivery
- •8.5 Suprachoroidal Drug Delivery
- •8.6 Summary
- •References
- •9.1 Introduction
- •9.2 Nonbiodegradable Ocular Drug Delivery Systems
- •9.2.1 Retisert
- •9.2.2 Ocusert
- •9.2.3 Vitrasert
- •9.2.4 I-vation
- •9.2.5 Iluvien
- •9.2.6 Nonbiodegradable Matrix Implants
- •9.2.6.2 Punctal Plugs
- •9.3 Medical Applications for Biodegradable Polymers
- •9.3.3 Poly(Ortho Esters)
- •9.3.4 Polyanhydrides
- •9.5.1 Ozurdex™
- •9.5.2 Surodex
- •9.5.3 Verisome
- •9.5.4 Lacrisert
- •9.6.1 Poly(Lactic Acid)-Based Implants
- •9.6.2 PLGA-Based Implants
- •9.6.5 Poly(Ortho Ester)-Based Implants
- •9.6.6 Polyanhydride-Based Implants
- •9.6.7 Other Biodegradable Polymer-Based Implants
- •9.7 Conclusions
- •References
- •10.1 Introduction
- •10.2 Manufacturing of Microparticles
- •10.3 Characterization of Microparticles
- •10.3.1 Morphological Characterization of Microparticles
- •10.3.2 Particle Size Analysis and Distribution
- •10.3.3 Infrared Absorption Spectrophotometry (IR)
- •10.3.4 Differential Scanning Calorimetry (DSC)
- •10.3.5 X-Ray Diffraction
- •10.3.6 Gel Permeation Chromatography (GPC)
- •10.3.7 Determination of Drug Loading Efficiency
- •10.3.8 “In Vitro” Release Studies
- •10.3.8.1 Additives in Microspheres
- •10.4 Sterilization of Microparticles
- •10.5 Calculation of the Dose of Microparticles for Injection
- •10.6 Injectability Studies
- •10.7 In Vivo Studies
- •10.7.1 In Vivo Injection of Microparticles
- •10.7.2 Ocular Disposition and Cellular Uptake
- •10.7.3 Tolerance of Microparticles
- •10.7.4 In Vivo Degradation of PLA and PLGA Microparticles
- •10.8 In Vitro and In Vivo Correlation
- •10.9 Microparticles for the Treatment of Posterior Segment Diseases. Animal Models and Human Studies
- •10.9.1 Proliferative Vitreoretinopathy (PVR)
- •10.9.2 Uveitis
- •10.9.3 Age-Related Macular Degeneration (AMD)
- •10.9.4 Diabetic Retinopathy
- •10.9.5 Macular edema
- •10.9.6 Acute Retinal Necrosis (ARN)
- •10.9.7 Cytomegalovirus (CMV) Retinitis
- •10.9.8 Choroidal Neovascularization
- •10.9.9 Diseases Affecting the Optic Nerve
- •10.9.11 Microparticles in Retinal Repair
- •10.10 Conclusions
- •References
- •11.1 Introduction
- •11.2 Nanoparticles
- •11.2.1 Polymer Nanoparticles
- •11.2.2 Liposomes and Lipid Nanoparticles
- •11.2.3 Micelles
- •11.2.4 Protein Nanoparticles
- •11.2.5 Carbohydrate Nanoparticles
- •11.2.6 Dendrimers
- •11.2.7 Combination Nanosystems
- •11.3 Using Nanotechnology to Improve Ocular Therapeutics
- •11.3.1 Improving Patient Compliance
- •11.3.2 Increasing Drug Retention and Sustained Release
- •11.3.3 Increasing Permeability and Tissue Partitioning
- •11.3.4 Targeting Nanotherapies
- •11.3.5 Intracellular Trafficking
- •11.4 Alternative Approaches to Improve Ocular Therapeutics
- •11.5 Conclusion
- •References
- •12.1 Introduction
- •12.2 Hydrogel Technology
- •12.6 Future Directions
- •References
- •13.1 Introduction
- •13.2 General Design Considerations
- •13.2.1 Administration Site
- •13.2.2 Body Design
- •13.2.3 Port Design
- •13.2.4 Vacuum and Pressure
- •13.2.5 Flushing and Fluid Replacement
- •13.2.5.1 Active Pumps
- •13.2.5.2 Passive Systems
- •13.2.5.3 Solid Refill
- •13.2.6 Contamination Potential
- •13.3 Historical Influences
- •13.3.1 Infusion Pumps
- •13.3.2 Glaucoma Drainage Devices
- •13.3.3 Pioneering of Refill Procedure in the Eye
- •13.4 Ophthalmic Refillable Devices
- •13.4.1 Invasiveness and Refilling Frequency
- •13.4.2 Intravitreal Delivery Through the Pars Plana
- •13.4.3 Episcleral Implantation for Trans-Scleral Delivery
- •13.4.4 Subretinal and Suprachoroidal Implantation
- •13.4.5 Lens Capsule Delivery
- •13.5 Conclusions
- •References
- •14.1 Introduction
- •14.2 Current Methods of Drug Delivery to the Eye
- •14.3 Improved Methods of Drug Delivery to the Eye Using Microneedles
- •14.3.1 Intrastromal Delivery to the Cornea Using Coated Microneedles
- •14.3.3 Suprachoroidal Delivery Using Hollow Microneedles
- •14.4 Microneedle Types and Other Applications
- •14.4.1 Poke and Apply
- •14.4.2 Coat and Poke
- •14.4.3 Poke and Release
- •14.4.4 Poke and Flow
- •14.5 Discussion
- •14.6 Conclusion
- •References
- •15.1 Introduction
- •15.1.1 General Mechanisms of Iontophoretic Drug Delivery
- •15.1.2 The Shunt Pathway
- •15.1.3 The Flip–Flop Gating Mechanism
- •15.1.4 Electro-Osmosis
- •15.2 Ocular Drug Delivery: The Past and the Future
- •15.3 Ophthalmic Applications of Iontophoresis
- •15.3.1 Transconjunctival Iontophoresis
- •15.3.1.1 Transconjunctival Iontophoresis of Antimitotics
- •15.3.1.2 Transconjunctival Iontophoresis of Anesthetics
- •15.3.2 Transcorneal Iontophoresis
- •15.3.2.1 Transcorneal of Fluorescein Iontophoresis for Aqueous Humor Dynamic Studies
- •15.3.2.2 Transcorneal Iontophoresis of Antibiotics
- •15.3.2.3 Transcorneal Iontophoresis of Antiviral Drugs
- •15.3.2.4 Other Drugs for Transcorneal Iontophoresis
- •15.3.2.5 Is Transcorneal Iontophoresis Safe?
- •15.4 Transscleral Iontophoresis
- •15.4.1 Transscleral Iontophoresis of Antibiotics
- •15.4.2 Transscleral Iontophoresis of Antiviral Drugs
- •15.4.3 Transscleral Iontophoresis of Anti-Inflammatory Drugs
- •15.4.3.1 Aspirin
- •15.4.3.2 Glucocorticoids
- •15.4.3.3 Transscleral Iontophoresis of Carboplatin
- •15.4.3.4 Is Transscleral Iontophoresis Safe?
- •15.4.3.5 Transscleral Iontophoresis for High Molecular Weight Compounds and Proteins
- •15.4.3.6 Clinical Application of Transscleral Iontophoresis
- •15.5 Applications of Iontophoresis to Ocular Gene Therapy
- •15.6 Future Developments
- •References
- •16.1 Introduction
- •16.2 Background
- •16.2.1 Intravitreal Injections
- •16.2.2 Impact of Genetics
- •16.3 Better Tools for Delivery and Treatment
- •16.3.1 Barriers to Success
- •16.3.2 Physics-Based Approaches
- •16.3.2.1 Physical Methods to Deliver Drugs to a Target Cell in the Posterior Segment
- •16.3.2.2 History of Electrical Fields in Medicine
- •16.3.2.3 Safety Concerns with Electric Fields
- •16.3.2.4 Definitions of Electric Field Methods
- •16.3.2.5 Advantages of Electric Fields for DNA Transfection vs. Viral Mediated DNA Delivery
- •16.3.2.6 Problems of In Vivo Electric Field Applications
- •16.3.2.7 Possible Strategies to Improve Electric Field-Mediated Drug Delivery
- •16.3.3 Experiences with Iontophoresis
- •16.3.3.1 Examples of Iontophoresis
- •16.3.3.2 Summary of the Strengths and Weaknesses of Iontophoresis
- •16.3.4 Experiences with Electroporation
- •16.3.4.1 Examples of Electroporation in Living Animals
- •16.3.4.2 Strengths and Weaknesses of Electroporation
- •16.4 Outstanding Issues in Electric Fields for the Delivery of Drugs
- •16.5 Summary
- •References
- •17.1 Introduction
- •17.2 Routes of Protein Administration
- •17.2.1 Topical
- •17.2.2 Intracameral
- •17.2.3 Intravitreal
- •17.2.4 Periocular (Transscleral)
- •17.2.5 Suprachoroidal
- •17.2.6 Subretinal
- •17.2.7 Systemic
- •17.3 Advantages and Challenges of Protein Delivery
- •17.4 Current Development Strategies
- •17.4.1 Pure Protein
- •17.4.2 PEGylation
- •17.4.4 Liposomes
- •17.4.5 Stem Cells
- •17.4.6 Implants
- •17.5 Case Studies
- •17.6 Ophthalmic Protein Formulation Development
- •17.6.1 Protein Biosynthesis
- •17.6.2 Preformulation Studies
- •17.6.3 Selection of Excipients
- •17.6.4 Optimization of Process Variables
- •17.7 Specifications and Regulatory Guidelines
- •17.8 Conclusions
- •References
- •18.1 Need for Suspension Development for the Back of the Eye
- •18.2 Background
- •18.3 Development of Drug Suspensions Intended for the Back of the Eye
- •18.3.1 Drug Suspensions
- •18.3.1.1 Physical Pharmacy Principles that Explain the Stability and Formulation of Suspensions
- •18.3.1.2 Formulation Methodology
- •18.3.1.3 Manufacturing Process
- •18.3.2 Factors To Be Considered in Suspension Development for the Back of the Eye
- •18.3.2.1 Formulation Development and Evaluation
- •18.3.2.2 In Situ Forming Suspensions, Selection of Drug Form for Suspension, and Polymeric Microparticle Suspension
- •18.3.2.3 Clinical Studies on Safety
- •18.4 Conclusions
- •References
- •19.1 Introduction
- •19.2 Drug Product Approval Process
- •19.3 Considerations for Back of the Eye Treatments
- •19.4 Adaptive Trial Design
- •19.5 Drug-Device Combinations
- •19.6 Product Summary Basis of Approval Reviews
- •19.6.1 OZURDEX™
- •19.6.2 LUCENTIS™
- •19.7 Summary
- •References
- •20.1 Background
- •20.2 FDA Endpoints
- •20.3 Endpoints for Neovascular Age-Related Macular Degeneration (Table 20.1)
- •20.4 FDA Guidelines for Other Retinal Diseases
- •20.5 Endpoint for Geographic Atrophy
- •20.6 Endpoint for Retinal Vein Occlusion
- •20.7 Future Endpoints
- •References
- •21.1 Introduction
- •21.2 Ocular Physiology and Pathology
- •21.2.1 Ocular Inflammation
- •21.2.2 Neovascularization
- •21.2.3 Degeneration
- •21.3 Current Therapies for Key Back of the Eye Disorders
- •21.3.1 Age-Related Macular Degeneration
- •21.3.1.1 Pathophysiology
- •21.3.1.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.3.1.3 Current Research Focused on Identifying New Targets
- •21.3.2 Diabetic Retinopathy
- •21.3.2.1 Pathophysiology
- •21.3.2.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.3.3 Retinopathy of Prematurity
- •21.3.3.1 Pathophysiology
- •21.3.3.2 Therapeutics Either in Current Use and in Clinical Trials
- •21.3.4 Degenerative Conditions
- •21.3.4.1 Pathophysiology
- •21.3.4.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.3.5 Opportunistic Infections
- •21.3.5.1 Pathophysiology
- •21.3.5.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.3.6 Autoimmune Disease
- •21.3.6.1 Pathophysiology
- •21.3.6.2 Therapeutics Either in Current Use or in Clinical Trials
- •21.4 Conclusion
- •References
- •22.1 Bile Acids as Anti-Apoptotic Neuroprotectants
- •22.3 Potential Need for Local Delivery of Bile Acids as Neuroprotectants
- •22.4 Preliminary Studies of Ocular Delivery of Bile Acids
- •22.5 Conclusion
- •References
- •Index
22 Development of Bile Acids as Anti-Apoptotic and Neuroprotective Agents… |
573 |
Acknowledgments Original work presented here was supported in part by The Abraham J. and Phyllis Katz Foundation, the Foundation Fighting Blindness (FFB), Research to Prevent Blindness (RPB), and NIH NEI grants R01EY014026, R01EY016470, R24EY017045, P30EY006360, and T32EY007092.
References
Amaral JD, Viana RJ, Ramalho RM, Steer CJ, Rodrigues CM (2009) Bile acids: regulation of apoptosis by ursodeoxycholic ccid. J Lipid Res 50:1721–1734
Arenas F, Hervias I, Uriz M, Joplin R, Prieto J, Medina JF (2008) Combination of ursodeoxycholic acid and glucocorticoids upregulates the AE2 alternate promoter in human liver cells. J Clin Investig 118:695–709
Arora SK, Faulkner A, Kim M, Ciavatta V, Pardue M (2009) Tudca preserves cones in fast degenerating Rd1 mice. Invest Ophthalmol Vis Sci 50:E-Abstract 978
Batta AK, Arora R, Salen G, Tint GS, Eskreis D, Katz S (1989) Characterization of serum and urinary bile acids in patients with primary biliary cirrhosis by gas-liquid chromatography-mass spectrometry: effect of ursodeoxycholic acid treatment. J Lipid Res 30:1953–1962
Batta AK, Salen G, Mirchandani R, Tint GS, Shefer S, Batta M, Abroon J, O’Brien CB, Senior JR (1993) Effect of long-term treatment with ursodiol on clinical and biochemical features and biliary bile acid metabolism in patients with primary biliary cirrhosis. Am J Gastroenterol 88:691–700
Boatright JH, Boyd AP, Sidney SS, Minear SC, Stewart RE, Chaudhury R, Ciavatta VT (2006a) Effect of tauroursodeoxycholic acid on light-induced retinal degeneration. ARVO Meet Abstr 47:4835
Boatright JH, Moring AG, McElroy C, Phillips MJ, Do VT, Chang B, Hawes NL, Boyd AP, Sidney SS, Stewart RE, Minear SC, Chaudhury R, Ciavatta VT, Rodrigues CM, Steer CJ, Nickerson JM, Pardue MT (2006b) Tool from ancient pharmacopoeia prevents vision loss. Mol Vis 12:1706–1714
Boatright JH, Nickerson JM, Moring AG, Pardue MT (2009a) Bile acids in treatment of ocular disease. J Ocul Biol Dis Infor 2:149–159
Boatright JH, Sidney SS, Kim ES, Nickerson JM, Edelhauser HF (2009b) Transscleral permeability of tauroursodeoxycholic acid. ARVO Meet Abstr 50:5958
Bowes C, Li T, Danciger M, Baxter LC, Applebury ML, Farber DB (1990) Retinal degeneration in the rd mouse is caused by a defect in the beta subunit of rod cGMP-phosphodiesterase. Nature 347:677–680
Castro RE, Sola S, Ramalho RM, Steer CJ, Rodrigues CM (2004) The bile acid tauroursodeoxycholic acid modulates phosphorylation and translocation of bad via phosphatidylinositol 3-kinase in glutamate-induced apoptosis of rat cortical neurons. J Pharmacol Exp Ther 311:845–852
Chang B, Hawes NL, Hurd RE, Davisson MT, Nusinowitz S, Heckenlively JR (2002) Retinal degeneration mutants in the mouse. Vis Res 42:517–525
Chang B, Hawes NL, Pardue MT, German AM, Hurd RE, Davisson MT, Nusinowitz S, Rengarajan K, Boyd AP, Sidney SS, Phillips MJ, Stewart RE, Chaudhury R, Nickerson JM, Heckenlively JR, Boatright JH (2007) Two mouse retinal degenerations caused by missense mutations in the beta-subunit of rod cGMP phosphodiesterase gene. Vis Res 47:624–633
Chen L, Dentchev T, Wong R, Hahn P, Wen R, Bennett J, Dunaief JL (2003) Increased expression of ceruloplasmin in the retina following photic injury. Mol Vis 9:151–158
Colak A, Kelten B, Sagmanligil A, Akdemir O, Karaoglan A, Sahan E, Celik O, Barut S (2008) Tauroursodeoxycholic acid and secondary damage after spinal cord injury in rats. J Clin Neurosci 15:665–671
Crosignani A, Battezzati PM, Setchell KD, Invernizzi P, Covini G, Zuin M, Podda M (1996) Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis. A dose-response study. Dig Dis Sci 41:809–815
574 |
S.L. Foster et al. |
Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90:537–548
Do VT, Nickerson JM, Boatright JH (2003) Prevention of apoptosis in an RPE carcinoma cell line by bile acids. ARVO Meet Abstr 44:4550
Duan WM, Rodrigues CM, Zhao LR, Steer CJ, Low WC (2002) Tauroursodeoxycholic acid improves the survival and function of nigral transplants in a rat model of Parkinson’s disease. Cell Transplant 11:195–205
Fedorowski T, Salen G, Calallilo A, Tint GS, Mosbach EH, Hall JC (1977) Metabolism of ursodeoxycholic acid in man. Gastroenterology 73:1131–1137
Fernandez-Sanchez L, Pinilla I, Campello L, Idiope M, Martin-Nieto J, Cuenca N (2008) Tauroursodeoxycholic acid (TUDCA) slows retinal degeneration in transgenic P23H rats. Invest Ophthalmol Vis Sci 49:E-Abstract 2195
Fernandez-Sanchez L, Lax P, Esquiva G, Pinilla I, Martín-Niet J, Cuenca N (2009) Loss of synaptic contacts in the retina is prevented by tauroursodeoxycholic acid (TUDCA) in transgenic P23H rats. Invest Ophthalmol Vis Sci 50:E-Abstract 980
Foster SL, Ziesel AC, Kendall C, Boatright JH (2009) Of mice and men: the search for polymorphisms in the SLCO1b2 gene. In: SURE program, Emory University, Atlanta, GA, p 20
Gargini C, Terzibasi E, Mazzoni F, Strettoi E (2007) Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study. J Comp Neurol 500:222–238 German Moring AJ, Nickerson JM, Boatright JH (2003) Protective effects of tauroursodeoxycholic acid against oxidative damage in human retinoblastoma cells. ARVO Meet Abstr 44:4551 Hofmann AF (1994) Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J
Gastroenterol 204:1–15
Hofmann AF (1999) The continuing importance of bile acids in liver and intestinal disease. Arch Intern Med 159:2647–2658
Invernizzi P, Setchell KD, Crosignani A, Battezzati PM, Larghi A, O’Connell NC, Podda M (1999) Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurineconjugated species in patients with primary biliary cirrhosis. Hepatology 29:320–327
Joo SS, Won TJ, Lee DI (2004) Potential role of ursodeoxycholic acid in suppression of nuclear factor kappa B in microglial cell line (BV-2). Arch Pharm Res 27:954–960
Keene CD, Rodrigues CM, Eich T, Linehan-Stieers C, Abt A, Kren BT, Steer CJ, Low WC (2001) A bile acid protects against motor and cognitive deficits and reduces striatal degeneration in the 3-nitropropionic acid model of Huntington’s disease. Exp Neurol 171:351–360
Kendall C, Premji SM, Stewart RE, Stewart RA, Boatright JH (2008) Ocular delivery of TUDCA provides neuroprotection in a mouse model of retinal degeneration. ARVO Meet Abstr 49:4932
Koga H, Sakisaka S, Ohishi M, Sata M, Tanikawa K (1997) Nuclear DNA fragmentation and expression of Bcl-2 in primary biliary cirrhosis. Hepatology 25:1077–1084
Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW, Bates GP (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493–506
Mulhern ML, Madson CJ, Thoreson W, Shinohara T (2008) Chemical chaperones and TUDCA partially suppress degeneration of retinal photoreceptor cells in transgenic mutant rhodopsin S334ter-3 rats. Invest Ophthalmol Vis Sci 49:E-Abstract 2038
Nakagawa M, Colombo C, Setchell KD (1990) Comprehensive study of the biliary bile acid composition of patients with cystic fibrosis and associated liver disease before and after UDCA administration. Hepatology 12:322–334
Oka H, Toda G, Ikeda Y, Hashimoto N, Hasumura Y, Kamimura T, Ohta Y, Tsuji T, Hattori N, Namihisa T et al (1990) A multi-center double-blind controlled trial of ursodeoxycholic acid for primary biliary cirrhosis. Gastroenterol Jpn 25:774–780
Oveson BC, Iwase T, Hackett SF, Lee SY, Usui S, Sedlak TW, Snyder SH, Campochiaro PA, Sung JU (2011) Constituents of bile, bilirubin and TUDCA, protect against oxidative stress-induced retinal degeneration. J Neurochem 116:144–153
22 Development of Bile Acids as Anti-Apoptotic and Neuroprotective Agents… |
575 |
Park IH, Kim MK, Kim SU (2008) Ursodeoxycholic acid prevents apoptosis of mouse sensory neurons induced by cisplatin by reducing P53 accumulation. Biochem Biophys Res Commun 377:1025–1030
Parquet M, Metman EH, Raizman A, Rambaud JC, Berthaux N, Infante R (1985) Bioavailability, gastrointestinal transit, solubilization and faecal excretion of ursodeoxycholic acid in man. Eur J Clin Investig 15:171–178
Parry GJ, Rodrigues CM, Aranha MM, Hilbert SJ, Davey C, Kelkar P, Low WC, Steer CJ (2010) Safety, tolerability, and cerebrospinal fluid penetration of ursodeoxycholic acid in patients with amyotrophic lateral sclerosis. Clin Neuropharmacol 33:17–21
Paumgartner G, Beuers U (2002) Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology 36:525–531
Phillips MJ, Walker TA, Choi HY, Faulkner AE, Kim MK, Sidney SS, Boyd AP, Nickerson JM, Boatright JH, Pardue MT (2008) Tauroursodeoxycholic acid preservation of photoreceptor structure and function in the rd10 mouse through postnatal day 30. Investig Ophthalmol Vis Sci 49:2148–2155
RamalhoRM,BorralhoPM,CastroRE,SolaS,SteerCJ,RodriguesCM(2006)Tauroursodeoxycholic acid modulates p53-mediated apoptosis in Alzheimer’s disease mutant neuroblastoma cells. J Neurochem 98:1610–1618
Ramalho RM, Viana RJ, Castro RE, Steer CJ, Low WC, Rodrigues CM (2008a) Apoptosis in transgenic mice expressing the P301L mutated form of human tau. Mol Med 14:309–317 Ramalho RM, Viana RJ, Low WC, Steer CJ, Rodrigues CM (2008b) Bile acids and apoptosis
modulation: an emerging role in experimental Alzheimer’s disease. Trends Mol Med 14:54–62
Reme CE, Grimm C, Hafezi F, Marti A, Wenzel A (1998) Apoptotic cell death in retinal degenerations. Prog Retin Eye Res 17:443–464
Rodrigues CM, Fan G, Wong PY, Kren BT, Steer CJ (1998) Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production. Mol Med 4:165–178
Rodrigues CM, Ma X, Linehan-Stieers C, Fan G, Kren BT, Steer CJ (1999) Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation. Cell Death Differ 6:842–854
Rodrigues CM, Stieers CL, Keene CD, Ma X, Kren BT, Low WC, Steer CJ (2000) Tauroursodeoxycholic acid partially prevents apoptosis induced by 3-nitropropionic acid: evidence for a mitochondrial pathway independent of the permeability transition. J Neurochem 75:2368–2379
Rodrigues CM, Sola S, Brito MA, Brondino CD, Brites D, Moura JJ (2001) Amyloid beta-peptide disrupts mitochondrial membrane lipid and protein structure: protective role of tauroursodeoxycholate. Biochem Biophys Res Commun 281:468–474
Rodrigues CM, Spellman SR, Sola S, Grande AW, Linehan-Stieers C, Low WC, Steer CJ (2002) Neuroprotection by a bile acid in an acute stroke model in the rat. J Cereb Blood Flow Metab 22:463–471
Rodrigues CM, Sola S, Nan Z, Castro RE, Ribeiro PS, Low WC, Steer CJ (2003a) Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats. Proc Natl Acad Sci USA 100:6087–6092
Rodrigues CM, Sola S, Sharpe JC, Moura JJ, Steer CJ (2003b) Tauroursodeoxycholic acid prevents Bax-induced membrane perturbation and cytochrome C release in isolated mitochondria. Biochemistry 42:3070–3080
Rubin RA, Kowalski TE, Khandelwal M, Malet PF (1994) Ursodiol for hepatobiliary disorders. Ann Intern Med 121:207–218
Setchell KD, Rodrigues CM, Podda M, Crosignani A (1996) Metabolism of orally administered tauroursodeoxycholic acid in patients with primary biliary cirrhosis. Gut 38:439–446
Sola S, Castro RE, Laires PA, Steer CJ, Rodrigues CM (2003) Tauroursodeoxycholic acid prevents amyloid-beta peptide-induced neuronal death via a phosphatidylinositol 3-kinase-dependent signaling pathway. Mol Med 9:226–234
576 |
S.L. Foster et al. |
Sola S, Aranha MM, Steer CJ, Rodrigues CM (2007) Game and players: mitochondrial apoptosis and the therapeutic potential of ursodeoxycholic acid. Curr Issues Mol Biol 9:123–138
Steinberg RH, Flannery JG, Naash M, Oh P, Matthes MT, Yasumura D, Lau-Villacorta C, Chen J, LaVail MM (1996) Transgenic rat models of inherited retinal degeneration caused by mutant opsin genes. Investig Ophthalmol Vis Sci 37:S698
Stiehl A, Rudolph G, Raedsch R, Moller B, Hopf U, Lotterer E, Bircher J, Folsch U, Klaus J, Endele R et al (1990) Ursodeoxycholic acid-induced changes of plasma and urinary bile acids in patients with primary biliary cirrhosis. Hepatology 12:492–497
Tint GS, Salen G, Colalillo A, Graber D, Verga D, Speck J, Shefer S (1982) Ursodeoxycholic acid: a safe and effective agent for dissolving cholesterol gallstones. Ann Intern Med 97:351–356
van de Steeg E, Wagenaar E, van der Kruijssen CM, Burggraaff JE, de Waart DR, Elferink RP, Kenworthy KE, Schinkel AH (2010) Organic anion transporting polypeptide 1a/1b-knockout mice provide insights into hepatic handling of bilirubin, bile acids, and drugs. J Clin Investig 120:2942–2952
Viana RJ, Nunes AF, Castro RE, Ramalho RM, Meyerson J, Fossati S, Ghiso J, Rostagno A, Rodrigues CM (2009) Tauroursodeoxycholic acid prevents E22Q Alzheimer’s Abeta toxicity in human cerebral endothelial cells. Cell Mol Life Sci 66:1094–1104
Walker S, Rudolph G, Raedsch R, Stiehl A (1992) Intestinal absorption of ursodeoxycholic acid in patients with extrahepatic biliary obstruction and bile drainage. Gastroenterology 102:810–815
Weitzel C, Stark D, Kullmann F, Scholmerich J, Holstege A, Falk W (2005) Ursodeoxycholic acid induced activation of the glucocorticoid receptor in primary rat hepatocytes. Eur J Gastroenterol Hepatol 17:169–177
Woo SJ, Kim JH, Yu HG (2010) Ursodeoxycholic acid and tauroursodeoxycholic acid suppress choroidal neovascularization in a laser-treated rat model. J Ocul Pharmacol Ther 26:223–229 Xiang X, Han Y, Neuvonen M, Pasanen MK, Kalliokoski A, Backman JT, Laitila J, Neuvonen PJ, Niemi M (2009) Effect of SLCO1B1 polymorphism on the plasma concentrations of bile acids
and bile acid synthesis marker in humans. Pharmacogenet Genomics 19:447–457
Yang ES, Kendall C, Premji SM, Boatright JH (2008) Tauroursodeoxycholic acid (TUDCA) prevents loss of visual function in rats. Invest Ophthalmol Vis Sci 49:E-Abstract 4933