Ocular Transporters in Ophthalmic Diseases and Drug Delivery

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INTRODUCTION......Page 17
AQUAPORIN EXPRESSION IN OCULAR TISSUES–INDIRECT EVIDENCE FOR A ROLE IN EYE PHYSIOLOGY......Page 18
ROLES OF AQUAPORINS IN MAMMALIAN PHYSIOLOGY DEDUCED FROM PHENOTYPES OF AQP-NULL MICE......Page 19
Aquaporin 1 and Cataract Formation......Page 21
Aquaporin 1 in Corneal Endothelium – its Role in Corneal Transparency......Page 22
Aquaporins and Ocular Surface Fluid Secretion......Page 24
Aquaporin 3 and Healing of Corneal Epithelial Wounds......Page 25
SUMMARY AND PERSPECTIVE......Page 27
REFERENCES......Page 28
OVERVIEW......Page 31
INVOLVEMENT OF ION TRANSPORT MECHANISMS IN MEDIATED RECEPTOR CONTROL OF CORNEAL EPITHELIAL CELL RENEWAL AND VOLUME REGULATION......Page 33
Na+/K+-Adenosine Triphosphatase (ATPase) and Na:K:2Cl Cotransporter......Page 36
K+/Cl- Cotransporter......Page 39
Na+/H+ and Cl-/HCO - Exchangers......Page 40
Plasma Membrane and Endoplasmic Reticulum (ER) Ca2+ Pumps......Page 41
Organic Ion Transporters......Page 42
K+ Channels......Page 46
Cl- Channels......Page 47
Voltage-Dependent Ca2+ Channels......Page 48
TRP Channels......Page 51
REFERENCES......Page 53
Function......Page 61
Transport......Page 62
Function......Page 63
Transport......Page 64
OCULAR SURFACE AND TEAR FILM......Page 65
FUTURE DIRECTIONS......Page 66
REFERENCES......Page 67
INTRODUCTION......Page 72
POSSIBLE MECHANISMS FOR THE SECRETION OF AQUEOUS HUMOR......Page 73
NA+ SECRETION......Page 74
HCO - SECRETION......Page 77
Na+-K+-2Cl- Symport Versus Parallel Cl-/HCO - and Na+/H+ Antiports......Page 79
Cl- Release from NPE Cells into the Posterior Chamber......Page 81
At the Stromal Surface of PE Cells......Page 83
Cyclic AMP......Page 84
A3 Adenosine Receptors (A3ARs)......Page 85
Nitric Oxide......Page 86
REFERENCES......Page 87
INTRODUCTION......Page 98
LENS STRUCTURE AND FUNCTION......Page 99
DIFFERENTIAL EXPRESSION OF MEMBRANE TRANSPORTERS IN THE LENS......Page 100
Diabetic Cataract: a Problem with Lens-Volume Regulation?......Page 105
Age-Related Nuclear (ARN) Cataract - a Transport Problem?......Page 110
Differential Expression of Nutrient Transporters in the Lens......Page 111
Nutrient Delivery to the Lens Nucleus via the Sutures......Page 113
A Model for Age-Related Nuclear Cataract......Page 114
REFERENCES......Page 115
SUMMARY......Page 120
NA, K-ATPASE DISTRIBUTION IN THE LENS......Page 121
LENS NA, K-ATPASE TURNOVER......Page 123
REGULATION OF LENS NA, K-ATPASE ACTIVITY......Page 125
LENS OSMOREGULATION AND OPACIFICATION......Page 126
REFERENCES......Page 130
PERICYTES AND CAPILLARY FUNCTION......Page 133
FUNCTIONAL SPECIALIZATIONS OF THE RETINAL MICROVASCULATURE......Page 134
EFFECTS OF DIABETES ON MICROVASCULAR KIR CHANNELS......Page 135
HYPERGLYCEMIA AND PERICYTE CHANNELS......Page 137
BREAKDOWN OF THE BLOOD–RETINAL BARRIER AND ION CHANNEL FUNCTION......Page 138
METABOLIC MODULATION OF MICROVASCULAR FUNCTION......Page 139
REFERENCES......Page 140
INTRODUCTION......Page 144
Glucose......Page 146
Lactate......Page 147
ANTIOXIDANT SUPPLY......Page 148
Cystine......Page 149
Leucine......Page 151
ADENOSINE TRANSPORT......Page 153
ATP-BINDING CASSETTE (ABC) TRANSPORTERS......Page 154
REFERENCES......Page 156
Regulation of Transport in the RPE......Page 160
TRANSPORT OF NUTRIENTS AND IONS FROM THE SUBRETINAL SPACE TO THE CHORIOCAPILLARIS......Page 161
MECHANISM OF TRANSPORT OF IONS IN RETINAL PIGMENT EPITHELIUM......Page 162
K+ AND Na+ CHANNELS......Page 166
Cyclic AMP-activated Cystic-Fibrosis Transmembrane Regulator (CFTR) Channels......Page 168
Calcium-Activated Cl Channels (CACL or CaCC)......Page 169
ELECTRONEUTRAL CATION-Cl- COTRANSPORTERS (SLC12)......Page 170
REGULATION OF [Cl-]I AND THE RELATIONSHIP WITH BICARBONATE TRANSPORTERS......Page 171
BICARBONATE TRANSPORTERS IN RETINAL PIGMENT EPITHELIUM AND FUNCTIONAL COUPLING TO OTHER RETINAL CELL LAYERS......Page 172
CARBONIC ANHYDRASES......Page 173
MONOCARBOXYLATE TRANSPORTERS (MCT)......Page 174
AQP1, AQP9 AND EDEMA......Page 175
BUFFERING OF IONS IN THE SUBRETINAL SPACE IN THE LIGHT-DARK CYCLE AND EXPLANATION OF ELECTRORETINOGRAM (ERG) C-WAVE AND DELAYED HYPERPOLARIZATION......Page 177
OTHER IMPORTANT RETINAL PIGMENT EPITHELIUM TRANSPORT MECHANISMS......Page 178
ACKNOWLEDGEMENTS......Page 179
REFERENCES......Page 180
SUMMARY......Page 188
PROPERTIES OF GLUCOSE TRANSPORTERS......Page 189
STRUCTURE OF THE OUTER BLOOD–RETINAL BARRIER......Page 190
Development of Tight Junctions in Chick Retinal Pigment Epithelium......Page 192
Expression of Glucose Transporters In Vivo......Page 194
Effect of the Neural Retina on the Expression of Glucose Transporters......Page 196
REFERENCES......Page 198
Ca2+-REGULATED FUNCTIONS OF THE RETINAL PIGMENT EPITHELIUM......Page 203
Voltage-Dependent Ca2+ Channels......Page 206
The Functional Role of Neuroendocrine L-Type Ca2+Channels in the Retinal Pigment Epithelium......Page 207
L-type Channels and Disease in the Retinal Pigment Epithelium......Page 209
TRP Channels......Page 210
SUMMARY......Page 211
REFERENCES......Page 212
INTRODUCTION......Page 219
FUNCTIONAL IMPORTANCE OF TAURINE IN THE RETINA......Page 220
TRANSPORT PATHWAYS FOR DELIVERY OF RETINAL TAURINE......Page 222
Taurine Transport by Retinal Pigment Epithelium......Page 224
AGEING OF THE TAURINE TRANSPORT SYSTEM: IMPLICATIONS FOR DISEASE......Page 226
CONCLUSIONS......Page 231
REFERENCES......Page 232
THE RETINAL PIGMENT EPITHELIUM......Page 236
P-GLYCOPROTEIN STRUCTURE......Page 237
P-GLYCOPROTEIN SUBSTRATES......Page 239
Inhibition of P-glycoprotein......Page 242
LOCALIZATION OF P-GLYCOPROTEIN IN THE RETINAL PIGMENT EPITHELIUM......Page 243
OCULAR SIDE-EFFECTS OF DRUGS......Page 244
DRUG DELIVERY......Page 245
REFERENCES......Page 246
INTRODUCTION......Page 255
Functional and Molecular Properties of the Rod Outer Segment Na+/Ca2+-K+ Exchanger......Page 256
Regulation of the Rod Na+/Ca2+-K+ Exchanger......Page 257
Interaction of the Na+/Ca2+-K+ Exchanger with other ROS Proteins......Page 258
Cloning and Analysis of Rod NCKX1 cDNAs......Page 259
Cloning and Analysis of a Second Retinal NCKX cDNA......Page 260
Post-translational Modification: Alternative Splicing, N-terminal Signal-peptide Cleavage and Glycosylation of NCKX1 and NCKX2......Page 261
Residues Important for Cation Transport......Page 264
Membrane Topology and Helix Packing of the NCKX2 Protein......Page 266
CONCLUSIONS......Page 267
REFERENCES......Page 268
INTRODUCTION......Page 272
EXCITATORY AMINO ACID TRANSPORTER (EAAT) LOCALIZATION......Page 273
DEVELOPMENTAL EXPRESSION......Page 276
Role in Synaptic Transmission......Page 277
Role in Gamma Aminobutyric Acid (GABA) Synthesis......Page 278
Interacting Proteins......Page 279
Excitatory Amino Acid Transporter Trafficking......Page 280
System N Transporters......Page 281
System L Transporters......Page 282
DISEASE INVOLVEMENT......Page 283
ACKNOWLEDGEMENTS......Page 284
REFERENCES......Page 285
SUMMARY......Page 290
NEUROTRANSMITTER TRANSPORTERS......Page 291
GABA TRANSPORTERS......Page 292
THE GABAERGIC SYSTEM IN THE RETINA......Page 293
GABA UPTAKE AND TRANSPORTERS IN THE RETINA......Page 295
GAT-1 in Ganglion Cells and/or Displaced Amacrine Cells......Page 296
GAT-1 in Amacrine Cells......Page 297
GAT-1 in Bipolar Cells......Page 300
GAT-1 in Horizontal Cells......Page 301
Summary of the Localization of GAT-1 in the Retina......Page 302
Regulation of GABA Receptor Activation by GAT-1 at Retinal Synapses......Page 303
GAT-1 and Retinal Development......Page 304
REFERENCES......Page 305
INTRODUCTION......Page 311
ABCR IS A MEMBER OF THE ATP BINDING CASSETTE (ABC) TRANSPORTER FAMILY......Page 312
CELLULAR TRANSPORT FUNCTION IN ABCR......Page 313
PROTEIN DOMAINS OF ABCR AND THEIR FUNCTIONS......Page 315
THE NUCLEOTIDE BINDING DOMAINS OF ABCR.......Page 316
ABCR-RELATED DEGENERATIVE MACULOPATHIES REPRESENT COMPLEX ETIOLOGIES: POTENTIAL DIRECTIONS FOR FUTURE RESEARCH......Page 317
REFERENCES......Page 319
GLUTAMATE TRANSPORTERS......Page 327
EAAT1......Page 328
EAAT5......Page 329
Ischemia......Page 330
Glaucoma......Page 332
Retinitis Pigmentosa......Page 333
Protein Kinases and Phosphatases......Page 334
Soluble factors......Page 336
Transporter Substrates......Page 338
ACKNOWLEDGMENTS......Page 339
REFERENCES......Page 340
INTRODUCTION......Page 348
THE IMPORTANCE OF GLUTAMATE TRANSPORT......Page 349
Excitatory Amino Acid Transporters in the Retina......Page 350
CHANGES IN GLUTAMATE HOMEOSTASIS IN THE RETINA DURING DIABETES......Page 355
MECHANISMS INVOLVED IN ALTERED GLUTAMATE FUNCTION......Page 358
Neuronal Dysfunction and Cell Death......Page 359
Abnormalities in Glutamate Transport as a Generalized Indicator of Müller Cell Dysfunction......Page 360
REFERENCES......Page 361
INTRODUCTION......Page 365
The Ocular Surface......Page 366
The Back of the Eye......Page 368
ENZYME DISTRIBUTION IN OCULAR TISSUES......Page 369
Cytochrome P450 Enzymes in the Eye......Page 370
Hydrolytic Enzymes......Page 371
Polymorphism......Page 372
Inhibition......Page 373
Induction......Page 374
Transporters......Page 375
Neurodegeneration......Page 376
DRUG TRANSPORTER–METABOLIC ENZYME INTERPLAY......Page 377
REFERENCES......Page 380
INTRODUCTION......Page 388
Cornea......Page 390
Bowman’s Layer......Page 391
Conjunctiva......Page 392
Posterior Segment......Page 393
Retinal Vessels......Page 394
Retinal Pigment Epithelium......Page 395
PHYSICOCHEMICAL PROPERTIES OF DRUGS AFFECTING PERMEABILITY ACROSS OCULAR BARRIERS......Page 396
EFFLUX PUMPS......Page 397
P-Glycoprotein......Page 398
REFERENCES......Page 399
Nanosystems......Page 403
Dendrimers......Page 404
Nanoplexes......Page 406
Liposomes......Page 407
MANUFACTURING METHODS FOR NANOPARTICLES......Page 408
NANOSURGERY......Page 409
Retinal Implants......Page 410
In Vivo Diagnosis......Page 411
Ex Vivo Diagnosis......Page 412
NANOTECHNOLOGY FOR GENE DELIVERY TO THE EYE......Page 413
NANOTECHNOLOGY FOR OCULAR DRUG DELIVERY......Page 415
TOXICITY CONCERNS WITH NANOTECHNOLOGY......Page 418
CONCLUSIONS......Page 419
REFERENCES......Page 420
CHEMISTRY AND BIOLOGIC FUNCTIONS OF ASCORBIC ACID (VITAMIN C)......Page 424
VITAMIN C AND THE RETINA......Page 426
Transporters for Ascorbate......Page 427
Transporters for DHAA......Page 428
The Blood–Retinal Barrier......Page 429
Neural Retina......Page 431
DIABETES AND RETINAL VITAMIN C STATUS......Page 432
CONCLUSIONS......Page 433
REFERENCES......Page 434
INTRODUCTION......Page 438
RATES OF TURNOVER......Page 439
SYSTEM OF EQUATIONS......Page 441
CONCLUSIONS AND PREDICTIONS FROM THE MATHEMATICAL MODEL......Page 443
REFERENCES......Page 444
back-matter.pdf......Page 446