PMID- 20238072
OWN - NLM
STAT- MEDLINE
DCOM- 20110912
LR  - 20200108
IS  - 0065-2598 (Print)
IS  - 0065-2598 (Linking)
VI  - 664
DP  - 2010
TI  - Adeno-associated virus serotype-9 mediated retinal outer plexiform layer 
      transduction is mainly through the photoreceptors.
PG  - 671-8
LID - 10.1007/978-1-4419-1399-9_77 [doi]
AB  - Due to its high ocular transduction, low immune clearance and capability to 
      bypass the brain blood barrier, adeno-associated virus-9 (AAV9) has been regarded 
      as a promising vector for retinal disease gene therapy. We recently demonstrated 
      that AAV9 efficiently transduces the retinal outer plexiform layer (OPL). The OPL 
      consists of synapses formed between axons of the rod and cone photoreceptors 
      (cell bodies in the outer nuclear layer, ONL) and dendrites of bipolar and 
      horizontal cells (cell bodies in the inner nuclear layer, INL). It is not clear 
      whether AAV9 transduces the OPL through the photoreceptors in the ONL or through 
      bipolar and horizontal cells in the INL. To map the subcelluar pathway(s) 
      involved in AAV9-mediated OPL transduction, we delivered subretinally 
      AAV9.CMV.eGFP, an AAV vector carrying the enhanced green fluorescent protein gene 
      (eGFP, 1 x 10(10) viral genome particles in microliter), to young (21-day-old) 
      and adult (2- to 3-month-old) C57BL/6 mice. Four weeks after subretinal 
      injection, eGFP expression was examined on retinal cryosections. PSD95 
      (postsynaptic density protein, a marker for photoreceptor terminals), CtBP2 
      (C-terminal binding protein 2, a marker for the photoreceptor synaptic ribbon), 
      PKCalpha (protein kinase Calpha, a marker for rod bipolar cells), and calbindin 
      (a marker for horizontal cells) were localized by immunofluorescence staining. In 
      AAV9 infected retina, eGFP expression was seen in the retinal pigment epithelia, 
      photoreceptor inner segments, ONL, OPL, Muller cells in the INL, inner plexiform 
      layer and ganglion cell layer. Interestingly, eGFP expression co-localized with 
      PSD95 and CtBP2, but not with PKCalpha and calbindin. Our results suggest that 
      AAV9 transduces the photoreceptor side of the synapses in the OPL rather than the 
      dendrites of bipolar and horizontal cells.
FAU - Lei, Bo
AU  - Lei B
AD  - Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China. bolei99@126.com
FAU - Zhang, Keqing
AU  - Zhang K
FAU - Yue, Yongping
AU  - Yue Y
FAU - Ghosh, Arkasubhra
AU  - Ghosh A
FAU - Duan, Dongsheng
AU  - Duan D
LA  - eng
GR  - R01 AR049419/AR/NIAMS NIH HHS/United States
GR  - AR49419/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Adv Exp Med Biol
JT  - Advances in experimental medicine and biology
JID - 0121103
RN  - 0 (enhanced green fluorescent protein)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Dependovirus/*classification/*genetics
MH  - Genetic Vectors/administration & dosage/genetics
MH  - Green Fluorescent Proteins/metabolism
MH  - Injections
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Photoreceptor Cells, Vertebrate/*metabolism/pathology
MH  - Serotyping
MH  - Subcellular Fractions/metabolism
MH  - *Transduction, Genetic
MH  - Tropism
EDAT- 2010/03/20 06:00
MHDA- 2011/09/13 06:00
CRDT- 2010/03/19 06:00
PHST- 2010/03/19 06:00 [entrez]
PHST- 2010/03/20 06:00 [pubmed]
PHST- 2011/09/13 06:00 [medline]
AID - 10.1007/978-1-4419-1399-9_77 [doi]
PST - ppublish
SO  - Adv Exp Med Biol. 2010;664:671-8. doi: 10.1007/978-1-4419-1399-9_77.