PMID- 15452082
OWN - NLM
STAT- MEDLINE
DCOM- 20041106
LR  - 20081121
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 45
IP  - 10
DP  - 2004 Oct
TI  - Photoreceptor protection by iris pigment epithelial transplantation transduced 
      with AAV-mediated brain-derived neurotrophic factor gene.
PG  - 3721-6
AB  - PURPOSE: To determine whether subretinal transplantation of iris pigment 
      epithelial (IPE) cells transduced with the adeno-associated virus (AAV2)-mediated 
      brain-derived neurotrophic factor (BDNF) gene can protect photoreceptors against 
      phototoxicity. METHODS: The BDNF gene was inserted into AAV2 (AAV2-BDNF), and the 
      recombinant AAV2 was transduced into rat IPE (AAV2-BDNF-IPE) cells at various 
      multiplicities of infection (MOI). The concentrations of AAV capsids and BDNF 
      were determined by enzyme-linked immunosorbent assay (ELISA). The AAV2-BDNF-IPE 
      cells were transplanted into the subretinal space of rats, and the rats were 
      placed under constant light on days 1 and 90 after the transplantation. The 
      thickness of the outer nuclear layer was measured in histologic sections and 
      compared to that of control sections. The expression of beta-galactosidase (LacZ) 
      in the subretinal space was confirmed by LacZ staining after AAV2-LacZ-IPE 
      transplantation. BDNF gene expression after transplantation was confirmed by 
      real-time polymerase chain reaction (PCR). RESULTS: Transduction efficiency 
      increased with successive days in culture and increased with higher MOI in vitro. 
      The expression of the BDNF gene in the subretinal space was higher in 
      AAV-BDNF-IPE than with AAV2-LacZ-IPE or with IPE-only transplantation. LacZ 
      expression was observed in the subretinal space 7 and 90 days after 
      transplantation. A statistically significant photoreceptor protection was 
      observed on days 1 and 90 in eyes receiving the AAV2-BDNF-IPE transplant, in both 
      the superior transplant site and the inferior hemispheres which did not receive 
      the transplant. CONCLUSIONS: Transplantation of AAV2-BDNF-IPE cells may be an 
      alternative method of delivering neurotrophic factors to the lesion.
FAU - Hojo, Masayoshi
AU  - Hojo M
AD  - Department of Ophthalmology and Visual Science, School of Medicine, Tohoku 
      University, Miyagi, Japan.
FAU - Abe, Toshiaki
AU  - Abe T
FAU - Sugano, Eriko
AU  - Sugano E
FAU - Yoshioka, Yuki
AU  - Yoshioka Y
FAU - Saigo, Yoko
AU  - Saigo Y
FAU - Tomita, Hiroshi
AU  - Tomita H
FAU - Wakusawa, Ryosuke
AU  - Wakusawa R
FAU - Tamai, Makoto
AU  - Tamai M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Cell Survival
MH  - Cell Transplantation
MH  - Dependovirus/*genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression
MH  - Genetic Vectors
MH  - Iris/*cytology
MH  - Light/adverse effects
MH  - Male
MH  - Photoreceptor Cells, Vertebrate/*radiation effects
MH  - Pigment Epithelium of Eye/metabolism/*transplantation
MH  - RNA, Messenger/metabolism
MH  - Radiation Injuries/etiology/*prevention & control
MH  - Radiation Protection
MH  - Rats
MH  - Rats, Long-Evans
MH  - Rats, Sprague-Dawley
MH  - Retina/radiation effects/*surgery
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transduction, Genetic
MH  - beta-Galactosidase/metabolism
EDAT- 2004/09/29 05:00
MHDA- 2004/11/09 09:00
CRDT- 2004/09/29 05:00
PHST- 2004/09/29 05:00 [pubmed]
PHST- 2004/11/09 09:00 [medline]
PHST- 2004/09/29 05:00 [entrez]
AID - 45/10/3721 [pii]
AID - 10.1167/iovs.04-0059 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3721-6. doi: 10.1167/iovs.04-0059.