- •Contents
- •Participants
- •Chair’s introduction
- •Gene therapy of retinal dystrophies: achievements, challenges and prospects
- •Discussion
- •Identifying retinal disease genes: how far have we come, how far do we have to go?
- •Discussion
- •Dominant cone and cone-rod dystrophies: functional analysis of mutations in retGC1 and GCAP1
- •Discussion
- •Isotretinoin treatment inhibits lipofuscin accumulation in a mouse model of recessive Stargardt’s macular degeneration
- •Discussion
- •The expanding roles of ABCA4 and CRB1 in inherited blindness
- •Discussion
- •What should a clinician know to be prepared for the advent of treatment of retinal dystrophies?
- •Discussion
- •Role of subunit assembly in autosomal dominant retinitis pigmentosa linked to mutations in peripherin 2
- •Discussion
- •The search for rod-dependent cone viability factors, secreted factors promoting cone viability
- •Discussion
- •Studies on retinal and retinal pigment epithelial gene expression
- •Discussion
- •From disease genes to cellular pathways: a progress report
- •Discussion
- •Prospects for gene therapy
- •Discussion
- •General discussion I
- •Range of retinal diseases potentially treatable by AAV-vectored gene therapy
- •Discussion
- •Gene therapy for Leber congenital amaurosis
- •Discussion
- •Index of contributors
- •Subject index
Index of contributors
Non-participating co-authors are indicated by asterisks. Entries in bold indicatepapers; other entries refer to discussion contributions.
A
Aguirre, G. 15, 35, 50, 64, 79, 80, 91, 93, 116, 162, 175, 176, 191, 203, 204, 205, 206
Ali, R. R. 13, 64, 127, 165, 173, 174, 175, 176, 189
B
Baehr, W. 49
*Barlow, C. 147
Bennett, J. 191, 195, 203, 204, 205, 206 *Berns, K. I. 179
Bhattacharya, S. S. 1, 33, 34, 37, 82, 92, 93, 162, 163
Bird, A. C. 28, 29, 30, 49, 65, 66, 67, 82, 85, 90, 91, 92, 93, 94, 161, 163, 173, 174, 178, 193, 203
Bok, D. 4, 14, 15, 34, 35, 63, 64, 65, 67, 80, 92, 113, 114, 116, 128, 161, 163, 174, 178
Bolz, H. 28, 81, 191
C
*Campochiaro, P. 131
*Carter, T. A. 147
Chader, G. J. 32, 35
*Chowers, I. 131
Cremers, F. P. M. 31, 65, 68, 79, 80, 81, 82,
83, 162, 163
D
Daiger, S. P. 17, 27, 28, 29, 30, 31, 32, 33, 34, 35, 81, 82, 83, 91, 114, 145, 146
*Deery, E. 37
*den Hollander, A. I. 68
Dryja, T. 29, 31, 34, 35, 65, 67, 83, 92, 93, 114, 115, 128, 129, 130, 161, 175
E
*Esumi, N. 131
F
Farber, D. B. 15, 28, 32, 35, 50, 93, 128, 145, 161, 162, 177
*Farjo, R. 147 *Fintz, A. C. 117 *Flannery, J. G. 179
Friedlander, M. 190, 191, 203, 204
G
Gal, A. 79, 94, 193, 205
*Ghosh, D. 147
H
Hauswirth, W. W. 12, 13, 64, 65, 91, 114, 127, 128, 161, 173, 174, 175, 179, 188, 189, 190, 191, 192, 193, 204, 205, 206
*Hero, A. 147 *Hoyng, C. B. 68 Hunt, D. M. 37, 49, 50
K
Kaleko, M. 27, 34, 35, 128, 129, 173, 174, 188, 189, 191, 192, 193, 202, 204
L
*Lambrou, G. 117
LaVail, M. M. 13, 14, 15, 79, 113, 127, 128, 129, 175, 179, 188, 190, 192, 204
208
INDEX OF CONTRIBUTORS
*Le¤veillard, T. 117
*Lewin, A. S. 179
*Li, Q. 179
*Liu, X. 51
*Loewen, C. J. R. 95
M
*Mata, N. L. 51
*Maugeri, A. 68
McInnes, R. 13, 14, 30, 31, 66, 80, 81, 82,
90, 113, 160, 173, 188
*Mears, A. J. 147
*Mohand-Sa|«d, S. 117
*Molday, L. L. 95
Molday, R. S. 35, 49, 95, 113, 114, 115, 116,
173
N
Nathans, J. 115, 127
*Newbold, R. 37
*Nusinowitz, S. 51
R
*Radu, R. A. 51
*Raisler, B. 179
S
Sahel, J-A. 67, 117, 127, 128, 129, 174, 175
209
Sieving, P. 92, 93, 94, 129, 174, 177, 178
Swaroop, A. 15, 30, 31, 32, 34, 65, 82, 129, 144, 145, 147, 160, 161, 162, 163, 164, 189, 190, 204
T
Thompson, D. 32, 35, 67, 94, 145, 146, 163,
178
*Timmers, A. M. 179
Travis, G. H. 31, 51, 63, 64, 65, 66, 67, 115, 127, 128, 129, 173, 178, 206
W
*Warren, M. J. 37
*Wilkie, S. E. 37
Y
*Yoshida, S. 147
*Yu, J. 147
Z
Zack, D. J. 14, 15, 29, 49, 65, 66, 67, 83, 92, 130, 131, 145, 146, 162, 163, 175, 189, 192, 203, 205
*Zhang, K. 37
Subject index
Page numbers in italics indicate tables.
A
A2E (N-retinylidene-N-retinylethanol-
amine) |
|
|
|
|
|
|
|
|
|
age-related macular degeneration |
65^66 |
||||||||
apoptosis, light-induced |
54 |
|
|
||||||
isotretinoin inhibition |
56^57, 59, 60^61 |
||||||||
phagolysosomes |
|
54 |
|
|
|
|
|||
secondary e¡ects |
65 |
|
|
|
|
||||
Stargardt disease |
53^54 |
|
|
|
|||||
A2PE-H2, isotretinoin inhibition |
56^57 |
||||||||
ABCA4 |
22 |
|
|
|
|
|
|
|
|
ABCA4 |
|
|
|
|
|
|
|
|
|
age-related macular degeneration |
33, 69 |
||||||||
autosomal recessive retinitis pigmentosa |
|||||||||
(ARRP) |
68, 69 |
|
|
|
|
||||
cone-rod dystrophy |
68, 69 |
|
|
||||||
founder e¡ects |
70^71 |
|
|
|
|||||
microarrays |
71^73 |
|
|
|
|
|
|||
normal individuals |
81 |
|
|
|
|||||
Stargardt disease |
52, 68, 69, 70^71 |
||||||||
ABCR |
|
|
|
|
|
|
|
|
|
GARP interaction |
|
115 |
|
|
|
||||
N-ret-PE £ippase function 53, 59, 68 |
|||||||||
peripherin interaction |
103, 113, 115 |
||||||||
rhodopsin regeneration |
53 |
|
|
||||||
abcr 52^53, 64 |
|
|
|
|
|
|
|
|
|
Accutane see isotretinoin |
|
|
|
|
|||||
acid^base balance |
36 |
|
|
|
|
|
|||
adeno-associated viral (AAV) vectors |
6, 166, |
||||||||
179^188 |
|
|
|
|
|
|
|
|
|
distal e¡ects |
13 |
|
|
|
|
|
|
|
|
extraocular injection |
188 |
|
|
||||||
intravitreal/subretinal injection |
188 |
||||||||
minigene 7 |
|
|
|
|
|
|
|
|
|
b-phosphodiesterase |
183 |
|
|
||||||
rho.rds |
166^167 |
|
|
|
|
|
|
||
targeting sequences |
204^205 |
|
|
||||||
transient bene¢ts |
167^168 |
|
|
||||||
tumorigenesis link |
12^13 |
|
|
||||||
adenoviral (AV) vectors |
6 |
|
|
|
|||||
gutted 6, 192 pseudotyped 190
A¡ymetrix GeneChips 151, 153
age-related macular degeneration (AMD) 52
A2E |
65^66 |
|
|
|
||
ABCA4 33, 69 |
|
|
|
|||
auto£uorescence |
66 |
|
|
|||
linkage disequilibrium |
33 |
|
||||
pathogenic mechanisms |
118 |
|
||||
phototoxicity 118^119 |
|
|
||||
prevalence |
148 |
|
|
|
||
rod loss |
119 |
|
|
|
||
vitamin A |
66 |
|
|
|
||
ageing, gene expression changes |
135 |
|||||
AIP (autocamtide-2-related inhibitory |
||||||
peptide) |
137 |
|
|
|
||
AIPL1 |
22 |
|
|
|
|
|
AIPL1 |
74 |
|
|
|
|
|
all-trans-retinaldehyde (atRAL) |
53, 59 |
|||||
allellic heterogeneity |
18 |
|
|
|||
amblyopia |
202^203 |
|
|
|
||
angiogenesis |
185 |
|
|
|
||
animal models, key issues |
1, 3 |
|
||||
apoptosis |
|
|
|
|
|
|
A2E |
54 |
|
|
|
|
|
Ca2+ |
47 |
|
|
|
|
|
therapy targeting |
21, 34^35, 150 |
|||||
astrocytes |
137 |
|
|
|
||
auto£uorescence
age-related macular degeneration 66 Stargardt disease 86, 93
type 1/type 2 dominant RP 87, 88, 92, 93 AxokineTM 9
B
Bardet^Biedl syndrome, gene identi¢cation
20
bioinformatics 2, 132, 134 blood^retinal barrier 191
bone-derived neurotrophic factor (BDNF) 9
210
SUBJECT INDEX
bone morphogenetic protein (Bmp) pathway 157
brain, retroaxonal transport to 188, 199 Briard dog 7^8
C
c-fos 9 c-Jun 136
C150S mutation 109 C214S mutation 105^106 C948Y mutation 75^76 Ca2+ 35, 37^38, 46^47, 50 Ca2+ blockers 47 cadherin 23 191^192 candidate genes 2^3, 33 caspase 47
CBA promoter 183^184, 190 cell cycling 14
cell death, temporality 87^88 cGMP 37, 38, 50
cGMP-gated channel/exchanger, peripherin
2/ROM1 complex interaction |
103^105 |
||||
chip^chip assays |
145 |
|
|
||
chip technology |
73, 82^83 |
|
|||
choroidal neovascularization 192, 193 |
|||||
choroideraemia |
31 |
|
|
|
|
chromosome 3 |
4 |
|
|
|
|
chromosome 7q |
2^3 |
|
|
||
ciliary neurotrophic factor (CNTF) |
8^10, 35, |
||||
168^169 |
|
|
|
|
|
bene¢ts |
125 |
|
|
|
|
CNTFRa |
9 |
|
|
|
|
downstream pathways |
15 |
|
|||
ganglion cells |
15 |
|
|
||
negative e¡ects 13^14 |
|
|
|||
P23H mutation |
10 |
|
|
||
P216L mutation |
9^10 |
|
|
||
photoreceptor survival |
9 |
|
|||
retinitis pigmentosa 9 |
|
|
|||
S334ter mutation |
10 |
|
|
||
side-e¡ects 169 |
|
|
|
||
spinal cord injury 14 |
|
|
|||
up-regulation |
129 |
|
|
||
Clarin 1 192 |
|
|
|
|
|
CLIA certi¢cation |
83 |
|
|
||
clinical heterogeneity 18, 28 |
|
||||
clinical settings |
88 |
|
|
|
|
CNTFRa 9 |
|
|
|
|
|
Coats-like exudative vasculopathy |
74^75 |
||||
Cods 161, 162 |
|
|
|
|
|
|
|
211 |
coiled-coils |
42, 44^46 |
|
COILS2 program 42 |
||
cone |
|
|
dystrophies |
37^49 |
|
rod loss link |
118 |
|
viability, rod-dependent factors 120, 121^ |
||
124 |
|
|
cone^rod dystrophies |
||
ABCA4 68, 69 |
||
GCAP1 and retGC1 37^49 |
||
conservation |
31^32 |
|
COS-1 cells |
123 |
|
costs, mutation detection 25, 26, 29^30, 83
CRB1 |
|
|
|
|
|
Crumbs |
69 |
|
|
|
|
localization 79, 80 |
|
|
|
||
CRB1 |
|
|
|
|
|
Coats-like exudative vasculopathy |
74^75 |
||||
genotype-phenotype correlation |
75^76 |
||||
Leber congenital amaurosis |
73^74, 75, 76 |
||||
RP12 |
69, 75, 76 |
|
|
|
|
Crb1 69 |
|
|
|
|
|
Crumbs |
69 |
|
|
|
|
CRX 133 |
|
|
|
|
|
CRX 74 |
|
|
|
|
|
Crx, Nrl interaction |
150 |
|
|
||
aA- and aB-crystallin |
136 |
|
|
||
cytochrome C 47 |
|
|
|
||
D |
|
|
|
|
|
deafness |
18, 28 |
|
|
|
|
diabetic retinopathy |
136, 185 |
|
|
||
diagnostic tests, standardized |
29 |
|
|||
diet 34, 66^67 |
|
|
|
||
diltiazem |
47 |
|
|
|
|
disease |
|
|
|
|
|
mechanisms 86^88 |
|
|
|||
registers |
88^89, 91 |
|
|
||
Drosophila |
69 |
|
|
|
|
drˇsen |
118 |
|
|
|
|
E |
|
|
|
|
|
early receptor potential (ERP) |
174 |
|
|||
electronic photoreceptor prosthesis |
148 |
||||
electrophysiology, therapeutic e¡ect |
|
||||
detection 88, 166 |
|
|
|||
encapsulated cell line |
125 |
|
|
||
endothelial progenitor cell transfection 190 ERK, phosphorylated (pERK) 9
212 |
|
|
|
|
|
ERK1 and ERK2 |
9 |
|
|
|
|
expressed sequence tags (ESTs) |
132, 134 |
||||
expression pro¢ling 131^144 |
|
|
|||
approaches 131^133, 151^153 |
|
||||
normal adult retina |
134^135 |
|
|||
retinal development |
133 |
|
|
||
retinal disease |
135^137 |
|
|
||
retinal pigment epithelium 137^142 |
|||||
extraocular injection 188 |
|
|
|
||
exudative vitreoretinopathy (EVR) |
193 |
||||
F |
|
|
|
|
|
FasL 137 |
|
|
|
|
|
¢broblast growth factor 2 (FGF2) |
|
||||
laser photocoagulation |
129 |
|
|
||
neovascularization risk |
125 |
|
|
||
outer nuclear layer |
15 |
|
|
|
|
phosphorylated ERK |
9 |
|
|
||
S334ter rats 10 |
|
|
|
|
|
¢broblast growth factor 18 (FGF18) |
15 |
||||
Foundation Fighting Blindness |
18, 32 |
||||
founder e¡ects 24, 25, 30, 70^71 |
|
||||
functional categories of genes |
21 |
|
|||
functional genomics, key issues |
1, 2 |
|
|||
FZD4 193 |
|
|
|
|
|
G |
|
|
|
|
|
G113E mutation |
108 |
|
|
|
|
GADD45 137 |
|
|
|
|
|
GADD153 137 |
|
|
|
|
|
gain of function |
86^87 |
|
|
|
|
ganglion cells, ciliary neurotrophic factor 15 Gap43 133
GARP
ABCR interaction 115 localization 115^116
peripherin 2/ROM1 complex interaction 103^105
phosphodiesterase interaction 105 role 115
GARP1 103, 116 GARP2 103, 105, 116 GCAP1 38, 46
functional analysis 40 gain of function 86 generation 40
retinal localization 39 GCAP2 38
phototransduction role 46
SUBJECT INDEX
retinal localization 39 GCAP3 38
retinal localization 39
gene augmentation therapy 182^184 gene-based pharmaceutical therapy 35 gene correction therapy 91^92
gene expression see expression pro¢ling
gene identi¢cation |
17^27, 86 |
|
|||
gene modi¢cation |
28 |
|
|||
gene replacement |
6^8 |
|
|||
gene therapy 4^12, 148^149, 165^172, |
|||||
179^188 |
|
|
|
||
dosage |
203^204 |
|
|||
key issues 1, 3 |
|
|
|||
large gene delivery problems |
205^206 |
||||
Leber congenital amaurosis |
195^202 |
||||
Usher syndrome |
191^192 |
|
|||
visual cortex |
203 |
|
|||
genetic heterogeneity 18 |
|
||||
genetics, key issues |
1, 2 |
|
|||
genotyping 85 |
|
|
|||
GFAP |
9 |
|
|
|
|
glaucoma, microarrays 137 |
|
||||
glial cell-derived neurotrophic factors |
|||||
(GDNF) |
123, 125, 184^185 |
||||
Gnat1 |
157 |
|
|
|
|
Gnat2 |
157 |
|
|
|
|
growth factors |
148, 150 |
|
|||
guanylate cyclase activating proteins |
|||||
(GCAPs) |
38^39 |
|
|||
GUCA1A 39 |
|
|
|
||
GUCY2D 22 |
|
|
|
||
GUCY2D 39, 74 |
|
|
|||
gutted vectors |
6, 192 |
|
|||
H |
|
|
|
|
|
haploinsu⁄ciency |
7, 86 |
|
|||
heat shock cognate protein 70 |
135 |
||||
heterogeneity |
18, 28 |
|
|||
HIPA |
91 |
|
|
|
|
HPRP3 |
21 |
|
|
|
|
HPRP3 |
25 |
|
|
|
|
Human Gene Mutation Database 21 human genome project 2
I
I-Gene microarrays 153^154, 157^158 immune privilege 191
IMPDH1 24, 25, 30
SUBJECT INDEX
incisures 115
inosine monophosphate dehydrogenase type
1 (IMPDH1) |
22, 23, 24, 136 |
|
||||||||
intraocular pressure elevation |
137 |
|
||||||||
IRBP |
128 |
|
|
|
|
|
|
|
|
|
ischaemia^reperfusion injury |
136 |
|
||||||||
isotretinoin (Accutane) |
35 |
|
|
|
||||||
A2E inhibition |
56^57, 59, 60^61 |
|
||||||||
alternatives |
65 |
|
|
|
|
|
|
|||
dose |
63^64 |
|
|
|
|
|
|
|
||
lipofuscin inhibition |
57, 60^61 |
|
||||||||
patient data |
177 |
|
|
|
|
|
|
|||
Stargardt disease |
51^63 |
|
|
|
||||||
J |
|
|
|
|
|
|
|
|
|
|
JAK (janus tyrosine kinase) pathway |
9 |
|||||||||
L |
|
|
|
|
|
|
|
|
|
|
L185P mutation |
106, 108 |
|
|
|
||||||
laser photocoagulation |
129^130 |
|
|
|||||||
Leber congenital amaurosis |
|
|
|
|||||||
blindness from birth |
28 |
|
|
|
||||||
CRB1 |
73^74, 75, 76 |
|
|
|
|
|||||
gene identi¢cation |
20, 22, 74 |
|
|
|||||||
gene therapy |
195^202 |
|
|
|
||||||
genotype/phenotype analysis |
79 |
|
||||||||
GUCY2D |
22, 39, 74 |
|
|
|
|
|||||
prevalence |
148 |
|
|
|
|
|
|
|||
retGC1 |
38, 42, 46 |
|
|
|
|
|
||||
RPE65 |
8, 22, 74, 196 |
|
|
|
|
|||||
lentivirus |
200 |
|
|
|
|
|
|
|
||
leukaemia inhibitory factor (LIF) |
8 |
|
||||||||
light toxicity |
118^119, 136 |
|
|
|
||||||
linkage disequilibrium |
33^34 |
|
|
|
||||||
lipofuscin |
|
|
|
|
|
|
|
|
|
|
abcr |
53 |
|
|
|
|
|
|
|
|
|
£uorescent component 53 |
|
|
|
|||||||
isotretinoin inhibition |
57, 60^61 |
|
||||||||
Stargardt disease |
52 |
|
|
|
|
|||||
loss of function |
86^87, 90 |
|
|
|
||||||
LRAT 178 |
|
|
|
|
|
|
|
|
||
M |
|
|
|
|
|
|
|
|
|
|
macular atrophy, retinitis pigmentosa |
28 |
|||||||||
macular degeneration, autosomal dominant,
gene identi¢cation |
20, 21 see also age- |
|
related macular degeneration |
||
melanin, inhibitory e¡ect |
137^138, 141 |
|
MERTK |
170, 171 |
|
Mertk 8 |
|
|
|
|
|
|
|
213 |
Merkt therapy |
170^171 |
|
|
||
microarrays 145, 151^153 |
|
|
|||
ABCA4 71^73 |
|
|
|||
advantages |
132 |
|
|
||
age-related gene expression changes |
135 |
||||
I-Gene |
153^154, 157^158 |
|
|
||
key issues 2 |
|
|
|||
limitations |
132 |
|
|
||
normal adult retina 134, 135 |
|
|
|||
redundancy |
146 |
|
|
||
retinal disease 136^137 |
|
|
|||
variability |
162 |
|
|
||
Mˇller cells 9, 189 |
|
|
|||
Mutation Database of Retina International |
|||||
21 |
|
|
|
|
|
Myo5a |
157 |
|
|
|
|
MYO7 |
21, 22 |
|
|
||
N |
|
|
|
|
|
N-methyl-d-aspartate (NMDA) |
137 |
|
|||
N-ret-PE (N-retinylidene- |
|
|
|||
phosphatidylethanolamine) |
53, 56, 59, |
||||
60, 68 |
|
|
|
||
neovascularization |
|
|
|||
blood^retinal barrier 191 |
|
|
|||
choroidal 192, 193 |
|
|
|||
¢broblast growth factor 2 (FGF2) |
125 |
||||
pigment epithelium derived factor (PEDF) |
|||||
|
185^186 |
|
|
||
nm23 |
136 |
|
|
|
|
nomenclature |
81^82 |
|
|
||
Norrie disease |
136, 193 |
|
|
||
NR2E3 |
161 |
|
|
|
|
Nr2e3 |
157 |
|
|
|
|
NRE |
150 |
|
|
|
|
NRL 25, 32, 150 |
|
|
|||
Nrl 150^151, 158, 160 |
|
|
|||
Nur77 |
137 |
|
|
|
|
nutrition |
34, 66^67 |
|
|
||
nystagmus 198 |
|
|
|||
O |
|
|
|
|
|
Oligotex |
139^41 |
|
|
||
OMIM |
21 |
|
|
|
|
Opn1sw |
157 |
|
|
|
|
optic nerve, glaucomatous 137 |
|
|
|||
optical coherence tomography (OCT) |
87, |
||||
92, 93 |
|
|
|
||
ORF (open reading frame)15 87 |
|
|
|||
214
P
P23, ribozymes 188 P23H
ciliary neurotrophic factor (CNTF) 10 prevalence 23, 24
ribozyme strategy 6^7 p45 160
P216L point mutation 7
ciliary neurotrophic factor (CNTF) 9^10 outer segments 108^109
temporal and spatial pro¢le 113 para-arteriolar preservation of retinal pigment
epithelium (PPRPE) 69, 75, 79 pathogenicity link 22^23
patient
handling 83^84 registers 88^89, 91
PCR
melanin inhibition 137^138, 141 qRT-PCR 153
peripherin 1 (RDS) 21, 24, 25 peripherin 2 95^112
ABCR interaction 103, 113, 115 autosomal dominant retinitis pigmentosa
(ADRP) 17, 96, 105^109
C-terminal domain |
|
97^98 |
|
C150S mutation |
109 |
||
C214S mutation |
105^106 |
||
L185P mutation |
106, 108 |
||
oligomeric structure |
99 |
||
outer segment disks |
95^96, 99, 101^103 |
||
P216L mutation |
108^109, 113 |
||
ROM1 interaction |
96, 99, 103^105 |
||
structural features |
|
97^98 |
|
topological model |
97 |
||
pH 36 phagocytosis 67 phagolysosomes 54
phenotype/genotype correlation 28^29 CRB1 75^76
diagnosis and management 2 Leber congenital amaurosis 79
phenotypic diversity 135 phenotypic heterogeneity 18 phosphodiesterase (PDE)
b subunit 182^183 cGMP 37, 38
GARP interaction 105 phosphorylated ERK (pERK) 9 photophobia 46, 49
SUBJECT INDEX
photopic retinal injury 136 photoreceptor
ciliary neurotrophic factor (CNTF) 9
CNTFRa |
9 |
|
prostheses |
148 |
|
recovery 38 |
|
|
transplantation |
119 |
|
phototoxicity |
118^119, 136 |
|
phototransduction |
35 |
|
PIG7 136 |
|
|
pigment epithelium derived factor (PEDF) 190, 192
CMV promoter driven 189
neovascularization |
185^186 |
retinopathy of prematurity 185, 190 |
|
VEGF blockade 189 |
|
polymorphisms 23, 33 |
|
pre-apoptotic signals |
150 |
preservation of para-arteriolar retinal pigment epithelium (PPRPE) 69, 75, 79
prevalence |
18^19, 23^24, 148 |
|
||
primate studies 15 |
|
|
||
proliferative diabetic retinopathy |
185 |
|||
prostheses |
148 |
|
|
|
PRPF8 |
21 |
|
|
|
PRPF31 |
21, 24, 25, 87 |
|
||
PRPF31 25 |
|
|
||
PRPH2 |
96 |
|
|
|
R |
|
|
|
|
ras-MAPK |
9 |
|
|
|
RCS rat |
8 |
|
|
|
Rcvrn 157 |
|
|
|
|
RDS (retinal degeneration slow) |
21 |
|||
autosomal dominant retinitis pigmentosa |
||||
22, 24 |
|
|
||
loss of function |
87, 90 |
|
||
RDS 21, 24, 25 |
|
|
||
rds/peripherin 7 |
|
|
||
RDS172 |
28 |
|
|
|
Recoverin |
157 |
|
|
|
redundancy |
146 |
|
|
|
registers |
88^89, 91 |
|
|
|
retGC1 |
|
|
|
|
activity |
39, 40 |
|
|
|
coiled-coils 42, 44^46 |
|
|||
cone^rod dystrophy 38 |
|
|||
domain structure |
40, 42 |
|
||
gain of function |
86 |
|
||
Leber congenital amaurosis 38, 42, 46
SUBJECT INDEX
peripherin 2 interaction 103 rods 49
retGC2 46, 49 11-cis-retinal 7
retinal detachment 174^175
retinal development, expression pro¢ling 133
retinal guanylate cyclase (retGC) 38 retinal pigment epithelium
gene augmentation therapy 184 gene expression 137^142
gene replacement 8 retinitis pigmentosa
ciliary neurotrophic factor (CNTF) 9 clinical heterogeneity 28
gene linkage 4
laser photocoagulation 129^130 MERTK 170, 171
microarrays 136 prevalence 148 RCS rat model 8 rhodopsin 5
RPE65 196
spontaneous mutations 27
retinitis pigmentosa, autosomal dominant gene identi¢cation 20, 21, 22
glial cell-derived neurotrophic factor (GDNF) 184^185
IMPDH1 22, 24, 25, 136 macular atrophy 28
mutation detection costs 25, 26 mutation identi¢cation 24^25 mutation prevalence 23^24 NRL 25, 150
peripherin 1 21 peripherin 2 96, 105^109
ribozyme therapy 6^7, 180^182
ROM1 96
type 1/type 2 87, 90^91, 92, 93 retinitis pigmentosa, autosomal recessive
(ARRP)
atypical, ABCA4 68, 69
CRB1 76
gene augmentation 182^183 gene identi¢cation 20 non-syndromic, usherin 21
retinitis pigmentosa, X-linked (XLRP) gene identi¢cation 20, 22
gene linkage 4 retinoblastoma 29, 137 retinoic acid pathway 158
215
retinoid cycling 177^178 11-cis-retinol 7
retinopathy of prematurity (ROP) Norrie gene mutation 193
pigment epithelium derived factor (PEDF)
|
|
185, 190 |
|
|
|
RetNet |
1, 19, 148, 195 |
|
|
||
retroaxonal transport 188 |
|
||||
retroviruses 12 |
|
|
|
||
RHO, reported mutations 22 |
|
||||
RHO |
24, 25 |
|
|
|
|
Rho |
157 |
|
|
|
|
rhodopsin |
|
|
|
||
ABCR 53 |
|
|
|
||
gene structure |
5 |
|
|
||
reported mutations |
21, 22 |
|
|||
retinitis pigmentosa |
5 |
|
|||
rhodopsin 4^5 |
|
|
|
||
rhodopsin kinase |
136 |
|
|
||
ribozyme therapy |
6^8, 180^182 |
|
|||
RNeasy 139^41 |
|
|
|
||
rods |
|
|
|
|
|
age-related macular degeneration |
119 |
||||
cone loss link |
118 |
|
|
||
cone viability factors |
120, 121^124 |
||||
Nrl |
150^151 |
|
|
|
|
retGC1 and retGC2 |
79 |
|
|||
ROM1 |
|
|
|
|
|
G113E mutation 108 |
|
||||
oligomeric structure |
99 |
|
|||
outer segment disks |
99, 101^103 |
|
|||
peripherin 2 interaction 96, 99, 103^105 |
|||||
structural features 97, 98 |
|
||||
Xenopus laevis |
103, 114 |
|
|||
ROM1 96 |
|
|
|
||
rough endoplasmic reticulum 87 |
|
||||
RP1 |
22, 23, 24 |
|
|
|
|
RP1 24, 25, 30 |
|
|
|
||
RP2 reported mutations 22 |
|
||||
RP10 |
|
136 |
|
|
|
RP10 |
24, 25 |
|
|
|
|
RP11 |
|
21, 28 |
|
|
|
RP11 |
25 |
|
|
|
|
RP12 |
|
|
|
|
|
Coats-like exudative vasculopathy |
75 |
||||
CRB1 69, 75, 76 |
|
|
|||
RP13 |
|
21 |
|
|
|
RP18 |
25 |
|
|
|
|
RPE65 |
|
|
|
|
|
AAV vector-based gene therapy 7^8, 183^184
216 |
|
|
|
RPE65 (cont.) |
|
|
|
Leber congenital amaurosis |
8, 22 |
|
|
reported mutations 22 |
|
|
|
retinoid cycling 178 |
|
|
|
RPE65 |
196^197 |
|
|
AAV vector-based gene therapy 170, |
|||
197^198 |
|
|
|
Leber congenital amaurosis |
74, 196 |
||
RPGRIP1 74 |
|
|
|
RPRG |
|
|
|
reported mutations 22 |
|
|
|
rough endoplasmic reticulum 87 |
|
||
RPRG 31 |
|
|
|
Rs1h 157 |
|
|
|
RT-PCR, melanin inhibition |
137^138, 141 |
||
S |
|
|
|
S cones |
161, 162 |
|
|
S334ter mutation |
|
|
|
ciliary neurotrophic factor (CNTF) |
10 |
||
¢broblast growth factor 2 (FGF2) |
10 |
||
glial cell-derived neurotrophic factor |
|||
(GDNF) 184^185 |
|
|
|
SAGE |
131^132, 134, 135 |
|
|
SCIDS |
12, 199 |
|
|
secreted Frizzled-related protein-2 (sFRP-2) 136
serial analysis of gene expression (SAGE) 131^132, 134, 135
severe combined immune de¢ciency (SCIDS) 12, 199
Shh 31^32
single nucleotide polymorphisms (SNPs) 23, 33
spinal cord injury 14 spontaneous mutations 27 Stargardt disease
A2E 53^54
ABCA4 52, 68, 69, 70^71 auto£uorescence 86, 93 carrier frequency 82 isotretinoin 51^63 lipofuscin 52
photoreceptor degeneration 64^65 vitamin A 67
SUBJECT INDEX
STAT pathway 9
STAT3 phosphorylation 9 stereology counting 120
subretinal space, vector placement 5^6, 188
survival factors |
148, 150 |
|
|
|
T |
|
|
|
|
terminology 81^82 |
|
|
||
tetracycline-controlled gene expression |
191 |
|||
tetraspanins 97 |
|
|
||
therapeutic e¡ect detection |
88, 166 |
|
||
TNF-R1 137 |
|
|
|
|
trabecular meshwork gene expression |
137 |
|||
transplantation |
119, 148 |
|
|
|
trans-splicing |
200 |
|
|
|
TRIzol |
138, 139^141 |
|
|
|
tumorigenesis, AAV vectors |
12^13 |
|
||
U |
|
|
|
|
USH1C |
22 |
|
|
|
USH2A |
22 |
|
|
|
USH2A 21 |
|
|
|
|
Usher syndrome |
|
|
||
gene identi¢cation 20, 21, 22 |
|
|||
gene therapy |
191^192 |
|
|
|
usherin |
21 |
|
|
|
V
VEGF blockade 189 velocity sedimentation 99 visual cortex 203
visual evoked cortical potentials 198 vitamin A 66^67
vitreous injection 188
W
Weri-Rb-1 137
Wnt/CA2+ pathway 157
X
Xenopus laevis 103, 114