Ординатура / Офтальмология / Английские материалы / Ocular Neuroprotection_Levin, Polo _2003
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demonstrate significance. The FDA has indicated that an active-treatment control trial “in which a finding of no difference between study drug and active-control would be considered evidence of effectiveness of the new agent.” It has also observed that such a design may be incapable in certain settings of allowing a conclusion to be drawn, due to the statistical difficulty of proving no difference. The FDA has not, however, as is commonly suggested, mandated the use of placebo for the study of new drugs. The risks of the use of placebo or no-treatment controls in specific diseases must be weighed against the risk that an activecontrol design may expose the subject to the risks of a trial without a reasonable chance to obtain useful information.
D.Financial Disclosure
Investigators who participate in clinical trials must disclose all financial ties to the sponsoring pharmaceutical company, whether relatively minor, such as limited honoraria for lectures; more substantial, such as ongoing consulting agreements, research grants or equipment purchases; or major, such as full-time employment by the company or equity interest in the company. Proprietary interest in a test product, such as patents, copyright, trademark, or licensing agreements must also be disclosed. Such disclosure must be reported to the IRB, the FDA, and may be required to be documented in the ICF. The FDA monitors data from investigators with such financial links extremely carefully.
In certain universities, potential conflict of interest or the appearance of such conflict is highly scrutinized. A positive financial disclosure by an investigator may prompt detailed review for such conflicts, and a determination as to whether the investigator may take part in a sponsored trial or whether he or she must sever all such financial ties during the conduct of the trial may be made by the university.
E.Reporting Adverse Events
Specific procedures are outlined in the CFR for reporting the occurrence of an adverse event during a clinical trial. Investigators must familiarize themselves and comply with these regulations.
BIBLIOGRAPHY
1.18th World Medical Assembly. World Medical Association Declaration of Helsinki: Recommendations guiding medical doctors in biomedical research involving human subjects. Helsinki, Finland, June 1964.
2.National Commission for the Protection of Human Subjects of Biomedical and Be-
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havioral Research. The Belmont Report: Ethical principles and guidelines for the protection of human subjects of research. OPRR Reports, April 18, 1979.
3.Code of Federal Regulations. Title 45 (45 CFR 46): Protection of Human Subjects. Revised June 18, 1991.
4.Code of Federal Regulations. Title 21 (21 CFR): Food and Drugs. Revised April 1, 1999.
5.FDA Information Sheets, October 1, 1995.
Index
Abducens nerve, 132, 133 Acepromazine, 24, 48, 52, 113 Acetazolamide, 51, 52, 121 Acinus, 227
Acridine orange, 210, 212 Ad libitum, 92, 130
Adeno-associated virus, 168, 170, 171, 174, 175, 176, 177, 180
Adenovirus, 62, 157, 158, 168, 170, 171, 172
Advanced Glaucoma Intervention Study, 281, 282, 297
Adverse event, 307, 308 Agarose, 98, 176
Age-related macular degeneration (ARMD), 110, 113, 199
Alpha-crystallin, 67
Alphagan (brimonidine), 50, 51 Amacrine cell, 7, 55, 66, 132, 192, 206,
219 Aminoguanidine, 159 Antiglaucoma, 50, 62 Antisense, 230
Apoptosis, 1, 85, 97, 98, 120, 169, 225, 226, 227, 230, 231, 234, 235, 241, 242, 243
Apoptosis initiation factor (AIF), 226, 227
Apoptosis protease activating factor-1 (APAF-1), 226
Apoptosome, 226
Applanation, 27, 40, 50, 51 Aquamount, 229, 231, 232, 233, 234,
235, 237
Aqueous humor, 23, 32, 33, 37, 39, 44, 45, 47, 57, 60, 72, 154
Arcuate, 62
Area centralis, 195, 213, 214, 218, 219 Argon laser, 32, 49, 50
Arrestin, 99
Artificial CSF, 209, 210, 211, 212 Ascorbate, 101, 102, 103 Ascorbic acid, 101, 102, 103 Aspartate, 2, 3
Astrocyte, 4, 67, 69, 111, 119, 175 Autofluorescence, 231, 232 Axoclamp, 213
Axon, 6, 13, 14, 16, 17, 18, 19, 23, 32, 43, 63, 66, 67, 69, 130, 131, 132, 133, 140, 141, 145, 146, 192, 206, 207, 209, 212, 213, 214, 215, 217, 242, 273, 275, 277, 278, 283
Axotomy, 133, 146, 169, 172, 242 Azimuthal, 197
Bandpass, 260
Basic fibroblast growth factor, 169 Bax, 226, 233, 237
Bcl-2, 99, 169, 237
Benzolamide, 121 Betaxolol (Betoptic), 155
313
314
Biomicroscopy, 51, 68
Bipolar cell, 207, 247, 253, 269, 277 Bisbenziamide, 234
Bistratified cell, 207, 275, 277 Blepharostat, 255, 257 BODIPY, 235
Brain-derived neurotrophic factor (BDNF), 3, 120, 156, 169, 217, 218, 219, 220
Bregma, 16, 19
Brimonidine (Alphagan), 50, 51, 62, 162, 299
Brn3a, 192
Brn3b, 192
Bullous, 113, 119, 122, 123 Buprenorphine, 68, 113
CA1, 147 Calbindin, 118, 192
Cannula, 38, 41, 42, 45, 114, 115, 144 Canthi, 255
Canthotomy, 36, 48 Capsid, 175 Carbocyanine, 133, 208
Carbonic anhydrase, 118, 121, 191 Carotenoids, 102
Caspase, 169, 226, 232 Cautery, 25, 68
CCD, 215
CD34, 179
Cecum, 161
Cell culture, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 173, 178, 234, 242, 244, 245, 246
Cell density, 4, 7, 190, 195, 196, 197, 200, 202, 219
Central retinal artery, 131 c-fos, 87, 99, 100
cGMP, 168 Chloromethyl-tetramethylrosamine
(CMTMR), 235, 236, 237, 238 Chondroitin, 67
Choriocapillaris, 110, 116
Choroid, 62, 66, 110, 111, 123, 131, 135, 136, 148, 154, 162, 210
Chromogen, 233
Chymotrypsin, 72
Index
Ciliary neurotrophic factor (CNTF), 3, 120, 169, 250
Cilioretinal, 299 c-jun, 100
Clinical trials, 99, 273, 274, 276, 279, 280, 281, 283, 284, 291, 292, 293, 294, 295, 296, 297, 298, 299, 303, 304, 305, 307, 309, 310
Cobalt chloride, 227, 229, 230 Co-culture, 4
Collaborative Initial Glaucoma Treatment Study (CIGTS), 281, 282, 283
Collagenase, 210
Cone photoreceptors, 62, 116, 117, 118, 121, 124, 190, 191, 192, 195, 199, 200, 251, 264, 265, 275
Confocal, 52, 69, 192, 193, 201, 214, 215, 228, 232, 238
Conjunctiva, 14, 26, 37, 257 Contamination, 8, 9, 154, 173, 177,
253, 261
Cornea, 5, 14, 27, 40, 42, 50, 51, 55, 60, 61, 114, 134, 136, 154, 155, 158, 250, 254, 255
Cosmid, 174
Cotransfection, 173, 176, 177, 179 Counterphase, 278, 279 Counterstain, 232
Coverslip, 134, 213, 229, 231, 232, 233, 234, 235, 237
Coxsackievirus, 172 Cribriform, 71 Cross-action forceps, 15 Cryosection, 191, 230 CsCl, 176
Culture media, 2, 3, 245 Cy5, 237 Cyanoacrylate, 117, 157 Cyclodialysis, 57, 60 Cyclopentolate, 113
Cynomologus monkey, 47, 48, 57, 61, 66, 69, 70, 116
Cystoid macular edema, 110, 122, 303 Cytochrome c, 226
Index
Cytochrome oxidase, 66
Cytomegalovirus, 172, 178
Cytotoxicity, 13, 171, 174
DAPI, 191, 232, 234, 238, 242, 243, 246, 247
Dehydroascorbic acid, 102 Dehydrogenase, 96, 230
Dendritic, 63, 207, 208, 209, 212, 214, 215, 216, 277, 278
Depo-Medrol, 68 Dexamethasone, 68, 69, 70, 130 Diaphorase, 66
DiAsp, 17, 19, 133, 139, 140, 142, 143, 144 Dichroic, 243, 244
Dihydroethidium (HEt), 243, 247 DiI, 208
Dimethyl sulfoxide (DMSO), 132, 202, 236, 244, 245
Dimethylformamide, 133 Dimethylthiourea (DMTU), 101, 102, 103 Disector, 199, 201
DNAse, 6 Docosahexaenoic acid, 3
Dorzolamide (Trusopt), 50, 51, 62 Dremel, 35
tool, 35
Dulbecco’s modified Eagles media (DMEM), 2, 3, 5
Dura, 17, 19, 68, 135, 137 dUTP, 229
Earclip, 255
Early Manifest Glaucoma Trial
(EMGT), 281, 282
Eclampsia, 111
Elastin, 67
Electrocardiogram, 250, 254
Electrode, 8, 19, 211, 212, 213, 251,
254, 255, 257, 267, 268
Electroretinogram (ERG), 54, 55, 95,
96, 97, 118, 119, 120, 145, 249,
250, 251, 252, 253, 254, 255,
257, 258, 259, 260, 261, 262,
263, 264, 265, 266, 267, 268,
269, 298
315
Embolization, 123
Encapsidation, 168, 171, 174, 176, 178 Endonuclease, 96, 227 Endophthalmitis, 156
Endothelin, 69 Enucleation, 154 Epifluorescence, 211, 212 Epiretinal, 122
Episclera, 24, 25, 26, 31, 32, 33, 34, 36, 39, 40, 45
episcleral vein, 24, 26, 31, 32, 33, 34, 36, 45
Episomal, 170, 172
Equiluminant, 278
Ethidium, 191, 245
Euthermic, 93, 94
Excitotoxicity, 3, 56, 61, 235, 279, 296, 299
Explant, 2, 5, 6, 9 cultures, 5, 6 Extracapsular, 114
Extracellular matrix, 1, 4, 5, 6, 67 Exudative, 110, 111, 199, 200
Fetal Bovine Serum (FBS), 5, 6 Fibroblast growth factor (FGF), 3, 120, 169 Fibronectin, 4
FK506, 161 Flavoprotein, 226
Fluorescein, 60, 117, 122, 139, 162 FluoroGold, 16, 17, 28, 132, 133, 139,
140, 141, 142, 144 Fluorophore, 16, 28, 132, 208, 237 Fluorophotometry, 57, 60 Flupirtine, 155, 156
Food and Drug Administration (FDA), 294, 303, 305, 306, 307, 308, 309, 310
Forceps, 4, 5, 14, 15, 25, 34, 36, 37, 38, 209, 210, 211
Forskolin, 62
Fovea, 52, 56, 63, 64, 86, 110, 121, 124, 190, 195, 196, 197, 202, 207, 211, 213, 214, 268, 274
Fundus, 51, 52, 53, 68, 113, 114, 134, 135, 136, 138, 144, 146, 155, 198
316
Funduscopy, 68
Fyrite, 9
Ganzfeld, 54, 95, 255, 257 GAPDH, 230, 231, 232, 237, 238 Gavage, 102, 159, 160, 161 Gavestinel, 296
GDx, 52, 298
GelMount, 229, 231, 232, 233, 234 Gene transfer, 28, 157, 167, 168, 169,
171, 173, 174, 175, 176, 178, 180
Glaucoma, 1, 23, 24, 28, 31, 32, 44, 45, 47, 48, 49, 50, 52, 53, 54, 55, 56, 57, 60, 61, 62, 63, 65, 66, 67, 69, 72, 147, 148, 153, 168, 169, 209, 214, 215, 273, 274, 275, 277, 278, 280, 281, 282, 283, 284, 294, 297, 298
hemifield test, 282
Glia, 6, 32, 51, 66, 67, 111, 119, 169, 172, 175, 253
fibrillary acidic protein (GFAP), 67, 119 -derived neurotrophic factor (GDNF),
120 Gliosis, 43, 120 Gliotic, 123
Glucocorticoid, 69, 70
Glutamate, 2, 3, 61, 119, 120, 235 Glutamine synthetase, 97, 119 Glyceraldehyde, 230
Glycine, 229, 231, 235, 296 Glycoprotein, 3
Golgi, 208 Gonioftal, 134 Goniolens, 48 Gonioscopic, 61
Green fluorescent protein (GFP), 178, 179
Growth factors, 1, 3, 6, 100, 155
Hanks balanced salt solution (HBSS), 5, 6, 8, 237, 245
Heidelberg retinal tomograph (HRT), 52, 298
Hemacytometer, 6
Index
Hematopoietic, 178, 179 Hemifield, 282, 283 Hemiretinal, 268
Henle, 202 Heparan, 67, 176 HEPES, 245 Herpesvirus, 177
HEt, 242, 243, 244, 245, 247 Heterologous, 180 Heterozygote, 99
High-Pass Resolution Perimetry (HPRP), 277, 278, 279, 280
Histochemistry, 118, 191 Hoechst dye, 8, 234 Homodimer, 191 Hyaluronic acid, 115, 117 Hyaluronidase, 112 Hydrogen peroxide, 228
Hydroxypropylmethylcellulose, 134 Hyperoxia, 120, 121 Hyperthermia, 91, 92, 93, 94
Hypertonic saline, 31, 32, 33, 34, 45 Hypertrophic, 111, 119
Hypotony, 33, 39, 40, 44, 49
Icosahedral, 171
Imaging software, 246, 247 MetaFluor, 244, 246 Metamorph, 193
Immune response, 23, 28, 171, 172, 173, 174, 176, 178
Immunoblotting, 232 Immunocytochemistry, 118, 132, 227,
230, 234, 236 Immunodeficient, 172, 179 Immunohistochemistry, 7, 119 Immunoreactivity, 65, 66 Immunoreagents, 202 Immunostaining, 66 Immunosuppression, 170, 173
In situ end labeling, 227, 228, 230, 231, 234, 235
Incubator settings, 5, 6, 7, 9, 236, 243, 244, 245
Infarction, 147
Inner plexiform layer, 54, 132, 146
Index
Innervation, 68 Insertional, 175, 178
Institutional review board (IRB), 292, 295, 303, 305, 306, 307, 308, 310
Integrin, 172 Interlaminar, 277
International Society for Clinical Electrophysiology of Vision (ISCEV), 254, 258, 260, 261, 264, 265, 266, 268
Interneurons, 192 Interphotoreceptor, 118 Intracameral, 69, 71 Intraconal, 68
Intraocular pressure (IOP), 23, 24, 26, 27, 28, 31, 32, 33, 36, 39, 40, 41, 42, 43, 44, 45, 48, 49, 50, 51, 52, 53, 54, 57, 60, 62, 63, 65, 66, 67, 68, 69, 70, 71, 72, 114, 122, 131, 133, 134, 135, 144, 145, 146, 147, 153, 169, 273, 281, 294, 297, 298, 299
Intraorbital, 14, 17, 131, 133, 140, 143 Intraperitoneal, 24, 130, 158, 161, 162 Intraretinal, 209, 212, 214 Intravenous, 123, 158, 162, 163 Intravitreal, 56, 112, 120, 121, 153, 155,
156, 157, 173, 175, 178, 250 Inverted terminal repeat, 174, 176 Iodixanol, 176
Iodoantipyrine, 61 Ionophore, 246
IOP measurement, 28, 40, 41, 70 Iridocyclitis, 49, 72 Iridolenticular, 51
Ischemic Optic Neuropathy Decompression Trial (IONDT), 296, 297
ISEL, 227, 228, 230, 231, 234, 235 Isoeccentricity, 198
Isofluorane, 68
Kainic acid, 7
Ketamine, 24, 48, 50, 51, 52, 113, 130, 136, 254
Koniocellular, 275
317
Lamina cribrosa, 50, 51, 64, 67 Laminin, 4, 5
Laser, 32, 48, 49, 50, 51, 52, 57, 60, 61, 62, 63, 69, 228, 232, 234, 237, 298
Latanoprost (Xalatan), 51, 62
Lateral geniculate nucleus (LGN), 4, 7, 14, 63, 64, 65, 66, 131, 275, 277, 278
Lectin, 4, 192
Lens, 5, 38, 40, 42, 48, 51, 72, 114, 116, 136, 146, 154, 156, 246, 254, 255, 257, 258, 268, 279
Lentivirus, 168, 170, 177 Light,
dark cycle, 39
damage, 9, 85, 86, 87, 88, 89, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103
exposure, 9, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 123
Limbus, 19, 24, 33, 34, 35, 36, 37, 38, 40, 113, 114, 134, 135, 136, 139, 156
Linoleic, 3, 5
Lipophilic, 17, 19, 102, 133
Long posterior ciliary artery, 33, 36 Long-terminal repeats, 177, 179, 180
Macaca mulatta, 48
Macula, 58, 59, 64, 109, 110, 113, 116, 117, 118, 123, 168, 169, 190, 193, 196, 197, 202, 266, 267, 269, 274, 297, 298
edema, 110 Maculopathy, 191, 199, 200
Magnocellular (M-cell), 63, 65, 275, 277, 278
Mannitol, 51, 52
Media supplements, 3, 8 Memantine, 61, 279, 296, 299 Metabotropic, 121
receptors, 121 Metamorphopsia, 110 Methohexital sodium, 48, 52
318
Methylene blue, 208 Methylprednisolone, 68 Microelectrode, 19, 210 Microgel, 69, 71
Microglia, 140, 142, 145, 175 Microinstruments, 35 Microneedle, 34, 35, 36, 44 Microscissors, 24 Microspheres, 69, 71, 123 Microsyringe, 136 Microvessel, 26
Minipumps, 69, 173
Mitochondria, 95, 225, 226, 227, 234, 235, 236, 237, 241, 242, 243, 244, 245, 246, 247
permeability transition pore, 236, 241
Mitomycin, 62 MitoTracker, 235, 236, 237 Monolayer cultures, 5
Morphometry, 95, 96, 97, 192, 201 Motoneurons, 132, 133
Mu¨ller cell, 111, 119, 120, 169, 170, 178, 192, 253
Multifocal ERG, 56, 57, 58, 62, 69, 118, 249, 266, 268, 269
Multifocal VEP, 57 Multipolar, 7 Mycoplasma, 8 Mydriatic, 52, 87, 88, 94 Myelin, 43, 116 Myocilin, 69
NADPH, 66 ND4, 212
Neovascularization, 26, 51, 110 Nernstian, 236
Nerve fiber analyzer, 298
Nerve growth factor, 3, 230, 235 Neurite, 2, 6, 7
Neurobasal, 3, 244 Neurobiotin, 212, 213, 215
Neurodegeneration, 47, 116, 168, 176 Neurofibrillar, 208
Neurofilament, 44
Neurogenetic, 192
Index
Neuroprotection, 1, 13, 16, 23, 28, 29, 31, 32, 44, 45, 61, 86, 100, 101, 103, 116, 120, 121, 123, 129, 130, 132, 136, 145, 146, 147, 148, 153, 155, 156, 157, 158, 159, 161, 162, 167, 168, 169, 170, 171, 172, 173, 175, 178, 179, 180, 189, 192, 193, 205, 206, 208, 215, 216, 217, 219, 220, 221, 273, 274, 276, 280, 284, 291, 294, 296, 297, 298, 299, 303
Neurotoxic, 249 Neurotracer, 16, 17
Neurotrophic factors, 100, 101, 129, 169, 173, 235
Neurotrophin, 3, 28, 100, 101, 168, 169, 172, 173
neurotrophin-3 (NT-3), 3 neurotrophin-4 (NT-4), 3
Nipradilol, 154, 155 Nitrergic, 66
Nitric oxide synthase (NOS), 159 NMDA, 56, 61, 296, 299 Nomarski, 193
Nonarteritic anterior ischemic optic neuropathy (NAION), 292, 296, 297
Nonresponder, 69, 70
Normal tension glaucoma (NTG), 31, 281 Normotensive, 58, 59
Normoxia, 120
Ocular Hypertension Treatment Study (OHTS), 279, 281, 283
Oculoplastic, 67 Oligodendrocyte, 175 Oligonucleosome, 227 Oligonucleotides, 230
Ophthalmic vessels ligature, 133, 134, 135, 136, 137, 138, 144, 146, 148
Ophthalmoscopy, 52, 67, 68, 69 Opponency, 277
Opsin, 7, 62, 118
Optic nerve crush, 15, 16, 161, 218, 220
Index
Optic nerve head, 14, 25, 32, 51, 56, 61, 64, 67, 69, 131, 137, 155
Optic nerve transection, 28, 53, 55, 57, 67, 68, 69, 133, 140
Optical coherence tomograph (OCT), 52, 298
Ora serrata, 209 Orbitotomy, 67, 68
Oscillatory potentials (OPs), 54, 56, 251, 252, 253, 254, 258, 259, 260, 261, 263, 265, 266, 269
Outer nuclear layer (ONL), 95, 96, 119, 148, 191, 200, 201
Outer plexiform layer (OPL), 54, 122, 146 Outflow, 23, 24, 32, 33, 39, 40, 44, 45, 49, 57, 60, 69, 112, 113
Overexpress, 99 Oversampling, 195
Palpebral, 48 Paracrystalline, 201 Parafilm, 229, 231, 232, 235
Paraformaldehyde, 18, 19, 139, 158, 213, 234, 237
Parafovea, 63, 190, 198 Parvalbumin, 66
Parvocellular (P-cell), 63, 65, 66, 275, 277, 278
Parvoviridae, 174
Pattern electroretinogram (PERG), 266, 267
PC12, 230 pClamp6, 217 Penumbra, 147 Pericyte, 111 Perifoveal, 59
Perimacular, 58, 59, 66
Perimetry, 52, 56, 57, 197, 274, 276, 277, 278, 280, 281, 283, 298
frequency-doubling technology (FDT), 278, 279, 280, 283
Perineural, 69
Periocular, 155 Peripapillary, 52, 53 Perivascular, 37
Permeability transition pore, 236, 241
319
Peroxidase, 233 PGF2α, 62
PGF2α-1-isopropylester, 50, 51 Phagocytosis, 63, 96, 99, 140, 225 Phenobarbital, 154
Phenylephrine, 52, 113
Phosphodiesterase, 168 Photoactivation, 123 Photochemically, 123 Photocoagulator, 123 Photoisomerized, 93
Photopic, 54, 56, 95, 119, 120, 251, 252, 253, 254, 258, 259, 260, 261, 263, 266
Photopigment, 261 Photoreceptor cultures, 7 Photostasis, 87 Photothrombosis, 123
Phototoxicity, 9, 85, 86, 87, 88, 89, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103
Pia mater, 132 Pigmentation, 87, 88 Pilocarpine, 62, 294 Planimetric, 190 Pneumotonography, 57 Pneumotonometry, 28, 51 Polarimeter, 52 Polyacrylamide, 69 poly-l-lysine, 3, 248 poly-l-ornithine, 3, 5
Polymerase chain reaction, 173 Potentiometric dye, 235, 236 Prelabel, 28, 208
Primary visual cortex, 19 Procaspase, 226 Proparacaine, 27 Propargylamines, 230 Proteinase, 228, 230, 235 Proteoglycan, 4, 67, 157, 176 Punctate, 140
Pyranine, 212 Pyruvate, 2
Radiolabeling, 154, 177 rds mouse, 168, 169, 250