Ординатура / Офтальмология / Английские материалы / Retinal Degeneration Disease_Hollyfield, Anderson, LaVail_1999

BDNF. See Brain-derived neurotrophic factor (BDNF)

Behavioral testing

circadian rhythm-based approach, 239-244 of mouse model vision, 169-172

for visual neural responses, 369 b5 null retina, 501

Beta2/NeuroD transcription factor, 155-160 and photoreceptor cell loss, 157f relationship to Bhlhb4, 156

role in pancreas, 159 scotopic ERGs with, 158-159

BHLH (basic helix loop helix) transcription factor, 155-160

Bhlhb4 transcription factor

and photoreceptor cell loss, 157f relationship to Beta2/NeuroD, 156 role in rods, 159

scotopic ERGs with, 158-159

Bietti crystalline corneoretinal dystrophy (BCD)

ERG of, 51t

genetic factors in, 49-52 lipid metabolism and, 50-52

Blindness

causes of, 133, 297, 303, 349 congenital, 9-13, 15, 89, 206 and POS phagocytosis, 499

Blood clots, 187 Blood vessels

abnormal. See Choroidal neovascularization (CNV)

aneurysms in. See Microaneurysms hemorrhage of, 196

occlusions of, 310-313, 399f retinal vessel attenuation, 96-97

See also specific vessels

Blotting techniques, 44-47, 250f Bmi1 repressor loss, 209-214

Bone marrow-derived stem cells (MSCs), 384-386

Brain-derived neurotrophic factor (BDNF) for neuroprotection, 447-449 transplantation of, 363-366

vitreous injections of, 297-301 Brain-derived stem cells (SCs), 384 Brain development, 211

Bruch’s membrane annexins in, 75-78

neuronal breaching of, 409f thickening of, 112-114

C

C-terminal segment, 285 Cadherins, 350-352f

CAIs. See Carbonic anhydrase inhibitors (CAIs)

Calbindin, 379-380 Candidate genes, 25-26

Capillary beds, 164-166, 165f, 167t Carbonic anhydrase inhibitors (CAIs)

applications for, 439 dose-dependence of, 441 effects of, 439-445, 442-443f for macular edema, 521-522

Caspase-3 activity, 333-336, 365, 449-450, 531

Cathepsin D (CatD), 267-268, 270-273 CD36 (lipid scavenger receptor), 499 Cell membranes

detergent-resistant, 491-495 G90D mutation in, 125-130, 127f permeability of, 64-67

retinoid transport across, 465-469 transmembrane proteins in, 179

Cells

acidification of, 414, 439, 444 amacrine, 379-380, 405-408, 409f astrocytes, 211

bipolar, 407-408

culture reagents for, 269 differentiation of, 155 embryonic stem (ESs), 173, 206 ganglion, 276-277, 405-406, 421

membranes of. See Cell membranes Müller glial cells, 209, 277-278, 327,

329-331, 405-407, 445

neural and retinal stem cells, 210-211, 377-380, 383

neural progenitor cells (NPCs), 211 programmed death of, 315

signals of, 275-280, 284, 335-336, 531-538 survival of, 6-7, 133, 150-151, 315-318,

337-340, 390, 434

toxic damage to, 63-67, 69-72, 291-294, 425-435

See also specific cells

Cellular acidification, 414, 439, 444 Cellular retinaldehyde-binding protein

(CRALBP), 477-481 characteristics of, 477

domain structural model, 478-479 and EBP50, 521

immunohistochemistry of, 212-214 ligand interactions in, 478-479 mutation-related diseases of, 477-478 protein interactions in, 479-481

Central polypurine tract (CPPT), 256 Central retinal artery occlusions (CRAOs),

310-313

Central retinal vein occlusions (CRVOs), 310-313

Cephalad fluid shifts, 417 Ceruloplasmin, 522 Chaperone function, 471-475 Chicken retina, 316-317

Choline aceytltransferase, 179, 183 Chondroitin sulfate, 365

Choroid

atrophy of, 57-60 neovascularization. See Choroidal

neovascularization (CNV) neuronal escape into, 409f

Choroidal neovascularization (CNV) in APOE4 TR-ch mice, 109-114 in diabetic retinopathy, 187 genetic factors in, 35-39

oxygen regulation of, 425 phototherapy for (PDT), 198-199, 297 VEGF and, 187-192, 303-306

Choroideremia histopathology of, 57, 60

optical coherence tomography (OCT) of, 57-60, 59f

Chromophore isolation, 104-106 Chromosomes

8q21-q22 (ROA1 locus), 21-26, 24f,

471-475 Xp21.1, 29

Ciliary margin zone (CMZ), 378 Ciliary neurotrophic factor (CNTF)

characteristics of, 147, 150, 212 effects on photoreceptors, 292 neuroprotection from, 331

Circadian rhythms

acrophase of, 241-242, 243f characteristics of, 411-412 defined, 240 photoentrainment of, 239-244

and susceptibility to light damage, 411-414 CME (cystoid macular edema), 310-313 CMZ (ciliary margin zone), 378

CNV. See Choroidal neovascularization (CNV)

Cochlear dysfunction, 341-347 Collagen X, 47

Colour vision, 23f, 439 Cone loss, 133, 315-318

Cone outer layer (COS), 125, 129 Cone-rod homeobox transcription factor

(CRX), 150-151

Cones

CAIs effect on, 441-445

conditional gene knockout system in, 173-177

cone-rod dystrophy, 10, 13 Cre expression in, 175-177 defined, 133

degeneration of, 90-91, 93, 105-106, 141, 143-144

delayed photoresponse in, 133-138 distribution and function of, 133, 176-177,

315

gene expression of, 147-151

hyperoxic effects on, 427f, 428, 431, 434 light flash response of, 83-84

microvilli ensheathing of, 519 photosensitivity of, 102-103 pigment regeneration in, 101-106 transcriptional regulation in, 151 of zebrafish, 201

See also Photoreceptors; Rods Congenital stationary night blindness

(CSNB), 125, 129, 159-160 Contrast sensitivity measurements, 170-172,

171f Corneas, 49-52, 51t

Corneoretinal dystrophy, 49-52, 51t Corticosteroids, 309-313

Cosmic rays, 422

CPPT (central polypurine tract), 256 CRALBP. See Cellular retinaldehyde-binding

protein (CRALBP)

CRAOs (central retinal artery occlusions), 310-313

Cre expression, 173-177

Cre/lox (conditional knockout) system, 173-177, 206

CRVOs (central retinal vein occlusions), 310-313

CRX (cone-rod homeobox) transcription factor, 150-151

Crystal deposits, 49-52

CSNB (congenital stationary night blindness), 125, 129, 159-160

Cyclic GMP phosphodierserase 6 (PDE6), 485-489

function and localization in photoreceptors, 487-489

interactions of, 485-487 structure of, 487

Cyclohexamide (CHI), 456-458

Cystoid macular edema (CME), 310-313 Cysts, intraretinal, 313f

Cytokines

effect on developing CNS, 279 examples of, 279

and retinal degeneration, 275-280 suppressors of cytokine signaling (SOCS),

275-280

See also specific cytokines

Cytoskeleton (actin), 351, 352f

D

Dark-adaptation, 125-126, 129f, 135f, 508-509 Deafness, 341, 349

Dendritic structure, 398-401 Detergent-resistant membranes (DRMs),

491-495

absence of phosphatase in, 493 fractionation and phosphorylation of, 492,

494f

DHA. See Docosa-hexaenoic acid (DHA) Diabetes mellitus (DM), 159, 187-192 Diabetic retinopathy (DR)

characteristics of, 195-196

laser photocoagulation for, 195-199 and neovascularization, 303-306 pathogenesis of, 163-167, 187-192

Discoidin (DS) domain, 284f, 285 DNA

injected for transgenesis, 203 plasmid construction, 268-269, 363 regulatory element of, 219-220

DNA tracings, 60f

Docosa-hexaenoic acid (DHA), 532-538 endogenous free, 533-535

for neuroprotection, 536-538 Dominant negative effect, 142-145 Dopamine, 70-71, 412-413

DRMs. See detergent-resistant membranes (DRMs)

Drosophila, 460-462 Drusen

annexins in, 75-78

and ApoE protein, 110, 112, 114

E

EAATs (excitatory amino acid transporters), 327

EBP50 (NHERF-1), 480-481 Edema

carbonic anhydrase inhibitors (CAIs) for, 439, 521-522

macular. See Macular edema

in retinitis pigmentosa (RP), 309-313 EGF (epithelial growth factor), 357-360 Electron micrographs (EMs)

of APOE TR mice retina, 113-114 of GABAergic amacrine cell, 409f of myosin VIIa labelling, 342-344

of normal versus abnormal RPE cells, 98f Electroretinograms (ERGs)

a-wave amplitudes in, 159, 286, 442-444 with AAV5-mOPs-RS1 treatment, 286 after BDNF injection and phototherapy,

301f

b-wave amplitudes in, 135-136f, 158-159, 177f, 283, 286, 441-444

of Bietti crystalline corneoretinal dystrophy (BCD), 51t, 52f

CAI effect on, 439-445, 442-443f changes with ischemia on, 330-331 of delayed photoresponse, 134-136 flash testing on

with CAIs onboard, 440, 442f with cell loss, 158f preparation for, 82

with subretinal injection, 252f flicker-type, 102f, 440-441, 442f, 443 fullfield and multifocal, 368

with MerTK, 120 normal response in, 24f of Rdh11 mice, 509f

rod and cone responses on, 83-84, 91f, 102f scotopic

of AMD, 122f

of BETA2/NeuroD cell loss, 158f of rod and cone responses, 102f

with subretinal implant, 322-323 Embryonic stem (ES) cells

versus adult (ASCs), 382-383 homologous gene-targeted, 173 of zebrafish, 206

Endoplasmic reticulum (ER) membrane, 284, 489f

Enhanced GFP (EGFP) reporter, 204-205 Enhancer trapping, 204

ENU (N-ethyl-N-nitrosourea), 95-97 Enzymatic activity. See specific enzymes EphA ephrins, 391-392

Episcleral vein, 399f

Epithelial growth factor (EGF), 357-360 ERGs. See Electroretinograms (ERGs) ERM-binding phosphoprotein 50 (EBP50),

480-481, 521

Excitatory amino acid transporters (EAATs), 327

Exons, 29-32

Eye extract, 180-181, 183 Eyes

adult human, 379-380

differences between species, 377-378 See also Animal models

F

FACS (fluorescence activated cell sorter) analysis, 269-270

FAK (focal adhesion kinase), 500-502 Farnesylation, 92

Fetal bovine serum (FBS), 513-517 Fetal retinal sheet transplants, 372-374

Filamin A (actin-binding protein), 351, 352f Fish retina. See under Animal models

FITC (fluorescein isothiocyanate), 358 Flowcharts

clinical for LCA, 17f

decisional for LCA diagnosis, 19f Fluorescein angiography

of Bietti crystalline corneoretinal dystrophy (BCD), 51f

of choroidal neovascularization, 37-38f of posterior pole atrophy, 58f

of retinal perfusion, 188-192

of vasoproliferative retinopathy, 188-192 Fluorescein isothiocyanate (FITC), 358 Fluorescence activated cell sorter (FACS)

analysis, 269-270 Fluorescence micrographs, 271f Fluorescent microscopy

A1E and ARPE-19 cells on, 66f of Cre expression, 175t

of myosin VIIa labelling, 342-343 Focal adhesion kinase (FAK), 500-502 Fovea centralis

adult-onset foveomacular dystrophy (AOFMD), 35-39

thickness of, 311-313 Functional titers, 258-259

Fundus changes (choroideremia), 57-60 Fundus photography

of Bietti crystalline corneoretinal dystrophy (BCD), 51f

of GFP expression, 262-263f of posterior pole atrophy, 58f

of retinal vessel attenuation, 96-97

G

G protein-coupled receptor kinase 1 (GRK1), 134-138

G90D (aspartic acid), 125-130 GABA-ergic inhibition, 409f GAL4-VP16 transactivator, 272 Ganglion cells, 276-277, 405-406, 421

GDNF (glial cell line-derived neurotrophic factor), 212

Gel electrophoresis

for molecular weight, 46f SDS-polyacrylamide (PAGE), 44-47

Gender, 6-7

Gene therapy (GT)

assessing efficacy of, 239-244 for LCA, 247-252

for neovascularization, 305 for retinoschisis, 285-288 viral vectors for, 305

Genes

AIPL1, 89-93 APOE, 110-114 b-PDE, 217-228

and a-PDE, 225-228 binding of, 221, 223 expression in, 217-218

functional testing of, 220-221 promotor, 218-228

transcriptional studies of, 218-225, 222f translational efficiency of, 225-228, 226f

bFGF/FGF2, 198-199 bHLH class B, 155-160

C1QTNF5, 41-47

assembly and stability testing of, 45-47 domain constructs for, 42-43 expression and purification of, 44 molecular size/weight of, 43, 46f

candidate, 25-26

CYP4V2, 49-52 exons of, 30-32

expression changes after photocoagulation, 198-199

expression regulation in, 217-228

INDEX

G90D (aspartic acid), 125-130 Gcgr (glucagon receptor gene), 170

GFAP, 198

Grk1, 134-138

GUCY2D, 16-18 HRGP-Cre, 173-177 hVEGF, 164-167

IMPDH1

enzymatic activity of, 82, 84 expression studies on, 82-85 photoreceptor degeneration in, 81-86 and retinal development, 84

LCA-related, 9-13, 15-19 Mertk, 95, 97

mutations of. See Genetic mutations

MYO7A, 341

PDGF, 198-199 peripherin/rds, 35-39

mutations in, 141-145 structure and function of, 145

and photoentrainment, 239-244 R26R (Cre-activatable lacZ reporter),

173-177

Rd1-Bmi1, 209-214

RdCVF, 316-318

RDH12 , 507-508

retinal delivery efficacy of, 255-264 RHO (rhodopsin), 233-238

RP1, 3-7, 6t

RPE65

and cone/rod responses, 102-103 and LCA, 247-252

mouse knockout, 240-244 therapeutic level in retina, 251 transgene expression, 249

RPGR mutations/deletions, 29-32 RS1, 284-288

characteristics of, 283-285 discoidin domain in, 284f, 285

silencing of, 233

siRNA design and screening, 234-235 thioredoxin-like 6 (TXNL6), 10-13 transcriptional regulation in, 217-228 transgene expression, 125-126, 249 USH1C, 341, 346

Usher 1 types of, 341-347

widely expressed essential, 176-177 Genetic heterogeneity

of C1QTNF5 gene, 42 of LCA, 9, 15-19, 16t

in proliferative retinopathy, 187-192

547

Genetic homozygosity, 23-24, 26 Genetic mutations

of AIPL1 gene, 89-93

Arg224Pro and Asp226Asn, 81-86 Arg677ter, 3-7

BEMr15 (r15) and BEMr (r18), 95-97 in CYP4V2 gene, 49-52 disease-linked missense, 284-285

of G90D, 125-130, 127f lakritz mutant, 205 LCA-related, 10-13, 15-19 P23H, 103-104 R172W+/+/rds+/+, 144

of RDS/peripherin gene, 35-39 and retinal degeneration, 169 of RP1 and RPO1, 3-7 Ser163Arg, 42

types of, 30-31 Tyr-141-Cys, 35-36, 39 X-linked in XLRP, 29-32

GFAP (glial fibrillary acidic protein), 288 GFP. See Green fluorescent protein (GFP) Glaucoma, 397-401

carbonic anhydrase inhibitors (CAIs) for, 439, 445

prevalence of, 397 vision loss from, 196

Glial cell line-derived neurotrophic factor (GDNF), 212

Glial cells, 209, 211-214, 379-380

Glial fibrillary acidic protein (GFAP), 288 Glutamate transport, 327-331

ERG of, 330-331 histological view of, 329f

Glutamine concentration, 406-407 Glycogen synthase kinase 3-b (GSK-3b),

205

Goldfish (Carrassius auratus) retina, 333-337, 390-392, 525-529

Gp130 (tyrosine kinase receptor), 147, 150-151

Graded retinopathy, 190t

Grafts, retinal, 369-374, 382, 392 Green fluorescent protein (GFP)

in ARPE-19 cells, 64-65 expression after AAV injection, 270

immunolabelled in subretinal space, 250f in RPE cells, 248-252

in vivo, 260-261, 262f

GRK-1 (G protein-coupled receptor kinase 1), 134-138

548

Growth factors

basic fibroblast growth factor (bFGF), 197-199, 357-360

epithelial growth factor (EGF), 357-360 PEDF. See Pigment epithelium-derived

growth factor (PEDF)

VEGF. See Vascular endothelial growth factor (VEGF)

GTPases, 487-489 Guanine nucleotides, 81

H

H2O2 treatment, 292-293 Haploinsufficiency, 142-145 Haplotypes

and gender, 6-7 for ROA1, 24-26 in trans, 4, 6

Harmonin, 341-347 isoforms of, 342f

localization of, 344-347, 345-346f and USH proteins, 349-352

Head tracking responses, 370-371 Hemorrhage, subretinal, 196

Hereditary disorders. See specific disorders HICD (hyperoxia-induced cell death),

428-434

High fat diets, 110-114 High-performance liquid chromatography

(HPLC), 70-72, 467f HIV-based vectors, 256

HPLC (high-performance liquid chromatography), 70-72, 467f

Human retinal pigment epithelium (hRPE) cell proliferation in, 514, 515f

VEGF synthesis in, 513-517 Hydrogen ions, 444 Hydrolysis, 468 Hyperlipoproteinemia, 112 Hyperoxia

effects on cones and rods, 427f, 428, 431, 434

retinal toxicity of, 425-435 sequence of events in, 428-430,

432-433

specificity to photoreceptors, 428-431, 433-434

Hyperoxia-induced cell death (HICD), 428-434

Hypertension, ocular. See Glaucoma Hypoglycemia, 170-172

INDEX

Hypoxia

HIF-1 and HRE activation in, 303 versus normoxia on RT-PCR, 181f, 184 photoreceptor vulnerability to, 425-435 retinal cell response to, 278-280

and retinal neovascularization, 163 and TJ protein expression, 179-184 and vascular endothelial growth factor

(VEGF), 198-199 Hypoxia-inducible factor (HIF-1), 303 Hypoxia response element (HRE), 303

I

Immunoblot analysis, 134, 137 Immunofluorescence microscopy

with AAV5-mOPs-RS1 treatment, 287 of myosin VIIa labelling, 342-343

of opsin antibody-stained retina, 148-150, 149f

Rdh11 expression on, 507 Implants, subretinal, 321-325 Inflammation/inflammatory mediators,

275-280, 537 Inner nuclear layer (INL)

exposed to space environment, 419-423

thickness of, 157f

Inner plexiform layer (IPL), 405-406, 420-422

Insulin

and detergent-resistant membrane rafts, 491-495

and photoreceptor degeneration, 155 role of, 159

See also Diabetic retinopathy (DR) Interferon gamma (IFNg), 176f, 275-278 Interleukin-4 (IL-4), 277-278 Intraocular injection procedure, 260 Intraocular pressure (IOP), 397-401, 422 Intraperitoneal injections, 440 Intravitreal injections

of AAV, 270

of acetazolamide, 444 of BDNF, 297-301 flash testing on, 252f procedure for, 260

of triamcinolone acetonide (TA), 309-313 IOP (intraocular pressure), 397-401, 422 IPL (inner plexiform layer), 405-406,

420-422

Irvine-Gass syndrome, 310-313

Ischemic retinopathy

aneurysm-related, 164-166, 165f, 167f, 309

occlusion-related, 187, 310-313, 339f and retinal glutamate transport, 327-331 retinal vessel attenuation, 96-97

See also Neovascularization (NV) Isoforms

E2, E3, and E4 encoding, 110-114 of harmonin, 341-342 neuron-specific b-tubulin III isoform

(TUJI), 399-401 Isomers, 71f, 72 Isorhodopsin, 105

J

JAK/STAT signal transduction pathway, 277f, 279

Janus kinase (JAK), 277-279

K

Kaplan-Meier survival analysis, 6-7 Knockout system

b5 knockout mouse, 120-122 Cre/lox, 173-177, 206

of exons, 30-32

versus knockdown in AIPL1, 91 of photoreceptor PDE6, 489

Rdh11 mice characterization, 508-509 Rpe65-/- mouse model, 240-244

Krypton lasers, 196

L

Labelling and staining immunolabelling and staining

with anti-TGN antibody, 527f with Dil, 399-400

of GFP and RPE65, 250f occludins in, 181-184

with TUJI antibodies, 399-401 TUNEL (terminal deoxynucleotidyl

transferase UTP nick end labelling) technique, 426-433

photolabelling of CRALBP, 478 Laser photocoagulation

of angiogenesis, 198-199 characteristics of, 196

for diabetic retinopathy (DR), 195-199 gene expression changes after, 198-199 histological changes after, 196-197 long-term effects of, 199

purpose of, 195 risks of, 197

Laser (Light Amplification by Stimulated Emmision of Radiation) treatments, 196

Late-onset retinal degeneration (L-ORD), 41-47

LD. See Light damage (LD)

Leber congenital amaurosis (LCA) and AIPL1 function, 475

clinical and molecular survey in, 15-19 ERG responses and histopathology in,

91f flowcharts of, 17f

gene therapy for, 247-252 and RDH12 gene, 507-508

rod-derived cone viability variants in, 9-13

role of AIPL1 in, 89-93 Lenses

as depot for INFg release, 275-276 LIF expression in, 148

Lentivirus (LV) characteristics of, 255-257 lentiviral vectors

design and biosafety of, 255-256 for gene therapy, 247-252 production of, 257-258

for retinal gene delivery, 255-264 targeting of, 256-257

Lentivirus-derived control vector (LV-RO.8- GFP), 248-252

LF. See Lipofuscin (LF)

LIF (leukemia inhibitory factor), 147-151 Light

adaptation studies, 125-126, 129f, 135f cycling of, 240-241

low-light sensitivity, 371-372

as phosphorylation trigger, 494-495 photoentrainment, 240-244

and phototransduction cascade, 505-506 Light-activated phosphorhodopsin (R*P),

459-460 Light damage (LD)

circadian-dependent, 411-414 longterm effects of, 407-408 methodology for induced, 406

Light-dependent translocation, 128-129 Light flashes/flash testing, 82-84, 135, 136f Light-induced retinal degeneration (LIRD)

model, 411-413

Light micrographs

of abnormal morphology, 183f of abnormal pigmentation, 97f

after BDNF injection and phototherapy, 298, 299f

of APOE TR mice retinas, 113-114 of BETA2/NeuroD cell loss, 157f of cones, 84f

of photoreceptor loss, 97f with subretinal implant, 324

Lipid metabolism

and ApoE protein, 110

and corneoretinal dystrophy, 50-52 Lipid rafts (“caveolae”), 491-495 Lipocortins. See Annexins (lipocortins) Lipofuscin (LF)

composition of, 79

in RPE (RPE LF), 63-67, 72-73 and RPE function, 120

LIRD (light-induced retinal degeneration) model, 411-413

Lizard (Ctenophorus ornatus) retina, 392-394 Loki analysis, 5f

Luciferase, 219, 222, 224

Luciferase assay system, 269-270, 272 LV. See Lentivirus (LV)

Lysine mutants, 457

M

Macrodeletion, 31-32 Macula lutea

adult-onset foveomacular dystrophy (AOFMD), 35-39

atrophy of, 283

degeneration of. See Macular degeneration edema of. See Macular edema

OCT through, 59f

in retinitis pigmentosa (RP), 309-313 Macular degeneration

genetic factors in, 63

X-linked retinoschisis (RS), 283-288

See also Age-related macular degeneration (AMD)

Macular dystrophy (MD) pathogenesis of, 144

and peripherin/rds mutations, 141, 143-144 and R172W, 142-143

Macular edema

carbonic anhydrase inhibitors (CAIs) for, 439, 521-522

clinically significant (CSME), 309-313

cystoid (CME), 310-313

in retinitis pigmentosa (RP), 309-313 Magnocellular pathways, 397-398, 401 Mean foveal thickness, 311f Melatonin, 412

Membrane blebbing, 64-67 Membranous whorls, 97, 98f Mer tyrosine kinase (MerTK)

receptors of, 120

in vitro phagocytosis, 499-500, 508 in vivo phagocytosis, 499-502, 501f

Metabolism, retinal, 413-414 Methazolamide, 444

Mice. See under Animal models Microaneurysms, 164-166, 165f, 167t, 309 Microarray analysis, 377-380 Microgravity, 419-423

Microneuromas, 406-408 Microvilli, apical, 99, 119, 519-523 Mission STS-72, 418-419

Mitochondrial RNA (ribonucleic acid) extraction of, 358-359

injected for transgenesis, 205 neurofilaments of, 401

in opsin, 413

Molecular size/weight determination, 43, 45, 46f

Müller glial cells buffering effect of, 445 characteristics of, 209

inflammatory stimulation of, 277-278 and retinal glutamate transport, 327,

329-331

seal formation of, 405-407 Mutations. See Genetic mutations

Myc-tagged (EQKLISEEDL) arrestin, 456, 459

Myosin VIIa

in apical processes, 520 binding properties of, 351, 352f and harmonin, 346

localization of, 343-344, 347 roles in Usher syndrome, 341-344

N

N-ethyl-N-nitrosourea (ENU), 95-97 N-retinylidene-N-retinylethanolamine (A2E),

536-537

NEDD8 ultimate buster (NUB1), 92-93, 472-474

Neonates, 449-450

Neovascularization (NV) animal models for, 163-167

in APOE4 TR-ch mice, 109-114 choroidal. See Choroidal

neovascularization (CNV) defined, 109, 163

and diabetic retinopathy (DR), 187-192, 303-306

histological views of, 191f therapies against, 303-306 and VEGF, 180-184

Neural cell markers, 359-360 Neural plasticity, 405-409

Neural progenitor cells (NPCs), 211

Neural retinal leucine (Nrl) zipper, 133-138, 148, 150-151

Neural stem cells (NSCs), 210-211 Neurite outgrowth, 528f

Neuron-specific b-tubulin III isoform (TUJI), 399-401

Neuronal migration, 407-408 Neuroprotectin D1 (NPD1)

identification and characterization of, 533, 537

neuroprotection of, 536-537 synthesis of, 531, 533-534, 537

Neuroprotection

with BDNF injections and transplantations, 297-301, 363-366, 447-449

and Bmi1 loss, 209-214 with CNPD1, 531-537 with CTNF, 331

by glutamate transport modulation, 327-331

by light activation of insulin receptor, 494 molecular mechanisms of, 291-294 PEDF for, 292-294

by preconditioning, 435 with RdCVFs, 316-318

by SOCS proteins, 275-280

with subretinal implants, 321-325 Neurotrophic factors/neurotrophins

in retinal cell differentiation, 357-360

and retinal ganglion cells (RGCs), 447-449 Night blindness. See Nyctalopia (night

blindness)

NIH.R3 Life Science Payload, 418 NMDA and AMPA mediation, 392-393 Norepinephrine, 70-72

NPCs (neural progenitor cells), 211 NPD1. See Neuroprotectin D1

Nr2e3 (nuclear receptor) transcription factor, 151

NRL (neural retina leucine) transcription factor, 133-138, 148, 150-151

NUB1 (NEDD8 ultimate buster), 92-93, 472-474

NV. See Neovascularization (NV) Nyctalopia (night blindness)

in choroideremia, 57

congenital (CNB), 125, 129, 159-160 in corneoretinal dystrophy, 49

in retinitis pigmentosa, 4

O

OA. See Optic atrophies (OAs) Observational (OB) protocol, 169-171

observer bias in, 170-172 Occludins, 179, 181-184 Occlusions. See Vein occlusions Oligonucleotide therapy, 304-305 Omega-3 fatty acids, 532

ONL. See Outer nuclear layer (ONL) Opsins (visual pigments)

function in cones, 137

M-opsin expression, 151, 175, 177 polyclonal anti-opsin (1D4), 127, 128f rhodopsin function, 102-106, 104f

in rods, 125-130

S-opsin expression, 175, 177 UV opsin promoter, 204

Optic atrophies (OAs)

autosomal dominant (DOA), 21 autosomal recessive (ROA1), 21-26

Optic axons, 525 Optic nerve (ON)

cell survival after injury (crush) to, 333-337, 447, 449

optical coherence tomography (OCT) through, 59f

regeneration of, 389-394

molecular prerequisites for, 391-392 role of training in, 392-394, 393f upregulation of TGN in, 525-529

Optical coherence tomography (OCT) after TA injection, 310-313

of choroideremia, 57-60, 59f of exon knockout, 32f

through optic nerve and macula, 59f Optokinetic testing, 128f

Optomotor responses, 169-172

Outer membrane protein 25 (OMP25), 346

Outer nuclear layer (ONL)

exposed to space environment, 419-423 of rods, 127-128

thickness of, 155-157, 287f, 299-301, 431 Oxidative stress, 531-538

and cell survival, 411, 535-537 and DHA, 532-533

Oxygen

and bronchopulmonary epithelium, 425 oxidative phosphorylation, 291-292 oxidative stress, 411, 531-538

See also Hyperoxia; Hypoxia Oxygen toxicity hypothesis, 426

P

Pancreas, 159, 187-192

Pars plana and pars plicata, 378 Particle titers, 258-260

PCR. See Polymerase chain reaction (PCR) PDE (phosphodiesterase) holoenzyme,

92-93

PDE6 (cyclic GMP phosphodierserase 6), 485-489

PDT. See Phototherapy (PDT) PDZ domains, 350-352, 480-481

PDZ proteins, 341-342, 344, 346, 350 PEDF. See Pigment epithelium-derived

growth factor (PEDF) Peripheral nerve grafting, 392 Phagocytes, 119-120 Phagocytosis

in photoreceptor outer segments (POS), 119-122

process of, 120-121

in vitro RPE, 97, 499-500, 508 in vivo RPE, 499-502

Phenotype-genotype correlations, 17-18 Phenotypes

function-related, 205-206 rescue of, 205

in transgenic mice, 144 Phospho-Akt (p-Akt), 333-337 Phospho-Bad (p-Bad), 333, 335-336 Phosphoinositide 3-kinase (P13K), 492 Phospholipids, 459-460, 461f Phosphorylation

characteristics of, 103 and GRK1, 137-138 light-dependent, 135 oxidative, 291-292 patterns of, 413

in rod degeneration, 105 tyrosine to ROS, 492-495

Photodynamic therapy (PDT), 297-301 See also Laser photocoagulation

Photoperiod reversal, 241-242 Photoreceptor outer segments (POSs)

DHA levels in, 531

exposed to space environment, 419-422 phagocytosis in, 119-122, 499-502

Photoreceptors age-dependency of, 136-138 AIPL1 in, 472-473

arrestin translocation in, 455-463, 458f and CAIs, 439-440

conditional gene knockout system in, 173-177

counts after subretinal implant, 324-325 Cre expression in, 175-177

damage to, 192 death of

after return to room air, 429-431, 430f characteristics of, 364, 365f

and macular deposits, 41-42 oxygen-induced, 425-435

sequence of, 428-430, 432-433, 435 degeneration of, 81-86, 95-99, 155-160 development of, 89

distribution and function of, 176-177 exposed to space environment, 417-423 G90D mutant opsin in, 125-130

gene therapy for, 283-288 hyperoxic specificity to, 428-431,

433-434

and hypoxia, 163, 278-280, 425-435 and laser photocoagulation, 198-199 light-induced lesions in, 405-409 neuroprotection of. See Neuroprotection nuclear layer of, 90

outer segment phagocytosis in, 119-122, 499-502

phagocytosis in, 499-502

and phototransduction cascade, 505-506 with Rd1-Bmi1 loss, 209-214

retinal hydrogenases in, 505-509, 506t role of ABCA4 in, 469

stem cell differentiation for, 383-386 transduction window for, 264 transplantation of, 316

and VEGF, 187-192 See also Cones; Rods Photosensitivity cells, 101