PMID- 17983616
OWN - NLM
STAT- MEDLINE
DCOM- 20080310
LR  - 20211020
IS  - 0014-4835 (Print)
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Linking)
VI  - 86
IP  - 1
DP  - 2008 Jan
TI  - BDNF-treated retinal progenitor sheets transplanted to degenerate rats: improved 
      restoration of visual function.
PG  - 92-104
AB  - The aim of this study was to evaluate the functional efficacy of retinal 
      progenitor cell (RPC) containing sheets with BDNF microspheres following 
      subretinal transplantation in a rat model of retinal degeneration. Sheets of E19 
      RPCs derived from human placental alkaline phosphatase (hPAP) expressing 
      transgenic rats were coated with poly-lactide-co-glycolide (PLGA) microspheres 
      containing brain-derived neurotrophic factor (BDNF) and transplanted into the 
      subretinal space of S334ter line 3 rhodopsin retinal degenerate rats. Controls 
      received transplants without BDNF or BDNF microspheres alone. Visual function was 
      monitored using optokinetic head-tracking behavior. Visually evoked responses to 
      varying light intensities were recorded from the superior colliculus (SC) by 
      electrophysiology at 60days after surgery. Frozen sections were studied by 
      immunohistochemistry for photoreceptor and synaptic markers. Visual head tracking 
      was significantly improved in rats that received BDNF-coated RPC sheets. 
      Relatively more BDNF-treated transplanted rats (80%) compared to non-BDNF 
      transplants (57%) responded to a "low light" intensity of 1cd/m2 in a confined SC 
      area. With bright light, the onset latency of SC responses was restored to a 
      nearly normal level in BDNF-treated transplants. No significant improvement was 
      observed in the BDNF-only and no surgery transgenic control rats. The bipolar 
      synaptic markers mGluR6 and PSD-95 showed normal distribution in transplants and 
      abnormal distribution of the host retina, both with or without BDNF treatment. 
      Red-green cones were significantly reduced in the host retina overlying the 
      transplant in the BDNF-treated group. In summary, BDNF coating improved the 
      functional efficacy of RPC grafts. The mechanism of the BDNF effects--either 
      promoting functional integration between the transplant and the host retina 
      and/or synergistic action with other putative humoral factors released by the 
      RPCs--still needs to be elucidated.
FAU - Seiler, Magdalene J
AU  - Seiler MJ
AD  - Ophthalmology-USC, Doheny, Los Angeles, CA, USA.
FAU - Thomas, Biju B
AU  - Thomas BB
FAU - Chen, Zhenhai
AU  - Chen Z
FAU - Arai, Shinichi
AU  - Arai S
FAU - Chadalavada, Sridhar
AU  - Chadalavada S
FAU - Mahoney, Melissa J
AU  - Mahoney MJ
FAU - Sadda, Srinivas R
AU  - Sadda SR
FAU - Aramant, Robert B
AU  - Aramant RB
LA  - eng
GR  - P30 EY003040/EY/NEI NIH HHS/United States
GR  - P30 EY003040-27/EY/NEI NIH HHS/United States
GR  - EY054375/EY/NEI NIH HHS/United States
GR  - EY03040/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071002
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Disease Models, Animal
MH  - Electrophysiology
MH  - Evoked Potentials, Visual
MH  - Head Movements
MH  - Microspheres
MH  - Motion Perception
MH  - Photic Stimulation/methods
MH  - Rats
MH  - Rats, Mutant Strains
MH  - Retina/cytology/*drug effects/pathology/*transplantation
MH  - Retinal Degeneration/pathology/physiopathology/psychology/*therapy
MH  - Stem Cell Transplantation/*methods
MH  - Stem Cells/drug effects
MH  - Superior Colliculi/drug effects/physiopathology
MH  - Treatment Outcome
PMC - PMC3074939
MID - NIHMS36724
COIS- MJS and RBA have a proprietary interest in the implantation instrument and 
      method.
EDAT- 2007/11/07 09:00
MHDA- 2008/03/11 09:00
PMCR- 2011/04/12
CRDT- 2007/11/07 09:00
PHST- 2007/06/01 00:00 [received]
PHST- 2007/08/28 00:00 [revised]
PHST- 2007/09/26 00:00 [accepted]
PHST- 2007/11/07 09:00 [pubmed]
PHST- 2008/03/11 09:00 [medline]
PHST- 2007/11/07 09:00 [entrez]
PHST- 2011/04/12 00:00 [pmc-release]
AID - S0014-4835(07)00276-X [pii]
AID - 10.1016/j.exer.2007.09.012 [doi]
PST - ppublish
SO  - Exp Eye Res. 2008 Jan;86(1):92-104. doi: 10.1016/j.exer.2007.09.012. Epub 2007 
      Oct 2.