PMID- 14691183
OWN - NLM
STAT- MEDLINE
DCOM- 20040120
LR  - 20220408
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 45
IP  - 1
DP  - 2004 Jan
TI  - Transplantation of Schwann cell line clones secreting GDNF or BDNF into the 
      retinas of dystrophic Royal College of Surgeons rats.
PG  - 267-74
AB  - PURPOSE: To assess the capacity of a retrovirus-engineered Schwann cell line 
      (SCTM41), transfected with either a glial cell line-derived neurotrophic factor 
      (GDNF) construct or a brain-derived neurotrophic factor (BDNF) construct, to 
      sustain visual function in the dystrophic Royal College of Surgeons (RCS) rat. 
      METHODS: Cell suspensions were injected into the subretinal space of the right 
      eye of 3-week-old dystrophic RCS rats through a transscleral approach. The left 
      eye remained as an unoperated control. Sham-surgery animals received injections 
      of carrier medium plus DNase to the right eye. All animals were placed on oral 
      cyclosporine. At 8, 12, 16, and 20 weeks of age, animals were placed in a 
      head-tracking apparatus and screened for their ability to track square-wave 
      gratings at various spatial frequencies (0.125, 0.25, and 0.5 cyc/deg). At the 
      end of the experiment, the animals were perfused and processed for histologic 
      assessment of photoreceptor survival. RESULTS: Animals with SCTM41-GDNF-secreting 
      cells, on average, head tracked longer than animals with SCTM41-BDNF-secreting 
      cells, and both performed better than those injected with the parent SCTM41 line. 
      All tracked longer than sham-surgery or nonsurgical dystrophic eyes. Each cell 
      type demonstrated preservation of photoreceptors up to at least 4 months of age, 
      over and above the sham-surgery control. CONCLUSIONS: Engineered Schwann cells 
      sustain retinal structure and function in the dystrophic RCS rat. Cells 
      overexpressing GDNF or BDNF had a greater effect on photoreceptor survival than 
      the parent line or sham surgery. This study demonstrates that ex vivo gene 
      therapy and subsequent cell transplantation can be effective in preserving 
      photoreceptors from the cell death that normally accompanies retinal 
      degeneration.
FAU - Lawrence, Jean M
AU  - Lawrence JM
AD  - Department of Pathology, Institute of Ophthalmology, London, United Kingdom. 
      jean.lawrence@ucl.ac.uk
FAU - Keegan, David J
AU  - Keegan DJ
FAU - Muir, Elizabeth M
AU  - Muir EM
FAU - Coffey, Peter J
AU  - Coffey PJ
FAU - Rogers, John H
AU  - Rogers JH
FAU - Wilby, Martin J
AU  - Wilby MJ
FAU - Fawcett, James W
AU  - Fawcett JW
FAU - Lund, Ray D
AU  - Lund RD
LA  - eng
GR  - EY 14038/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cell Line
MH  - Cell Survival
MH  - Cell Transplantation
MH  - Clone Cells
MH  - Gene Transfer Techniques
MH  - Genetic Vectors
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Head Movements/physiology
MH  - Nerve Growth Factors/genetics/*metabolism
MH  - Photoreceptor Cells, Vertebrate/pathology
MH  - Rats
MH  - Rats, Mutant Strains
MH  - Retinal Degeneration/metabolism/pathology/*surgery
MH  - Retroviridae/genetics
MH  - Schwann Cells/*metabolism/*transplantation
MH  - Vision, Ocular/physiology
EDAT- 2003/12/24 05:00
MHDA- 2004/01/21 05:00
CRDT- 2003/12/24 05:00
PHST- 2003/12/24 05:00 [pubmed]
PHST- 2004/01/21 05:00 [medline]
PHST- 2003/12/24 05:00 [entrez]
AID - 10.1167/iovs.03-0093 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2004 Jan;45(1):267-74. doi: 10.1167/iovs.03-0093.