PMID- 8069702
OWN - NLM
STAT- MEDLINE
DCOM- 19940926
LR  - 20220310
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 647
IP  - 1
DP  - 1994 May 30
TI  - Retinal ganglion cell survival is promoted by genetically modified astrocytes 
      designed to secrete brain-derived neurotrophic factor (BDNF).
PG  - 30-6
AB  - Genetically engineered cells carrying genes for neurotrophic factors have 
      potential application for treatment of neurodegenerative diseases and injuries to 
      the nervous system. Brain-derived neurotrophic factor (BDNF) promotes the 
      survival of specific neurons, including retinal ganglion cells (RGC). To 
      determine whether genetically engineered astrocytes might be used for delivering 
      bioactive BDNF, we infected primary type 1 rat astrocytes with a retrovirus 
      harboring a human prepro-BDNF cDNA and assayed the medium conditioned by these 
      astrocytes for effects on survival of rat RGCs in vitro. High levels of BDNF mRNA 
      were expressed by infected astrocytes, but not by control astrocytes as 
      determined by RNase protection assay using a BDNF specific probe. To test for 
      secretion of bioactive BDNF from the transgenic astrocytes, embryonic day 17 rat 
      retinas were dissociated and grown in medium conditioned (CM) for 24 h by 
      astrocytes infected with a replication deficient retrovirus carrying BDNF, NGF, 
      or alkaline phosphatase (AP) cDNA. After 3 days, the number of Thy-1 
      immunoreactive RGCs was counted. BDNF astrocyte CM significantly enhanced RGC 
      survival by 15-fold compared to the AP control. NGF astrocyte CM had no 
      significant effect. The rate of BDNF secretion was estimated at 83-166 pg/10(5) 
      cells/h. This study demonstrates that astrocytes can be genetically engineered to 
      synthesize and secrete bioactive BDNF. These techniques may be applicable to 
      rescuing neurons from degenerative processes and also for enhancing their 
      survival following transplantation.
FAU - Castillo, B Jr
AU  - Castillo B Jr
AD  - Department of Neurobiology and Anatomy, University of Rochester Medical Center, 
      NY 14642.
FAU - del Cerro, M
AU  - del Cerro M
FAU - Breakefield, X O
AU  - Breakefield XO
FAU - Frim, D M
AU  - Frim DM
FAU - Barnstable, C J
AU  - Barnstable CJ
FAU - Dean, D O
AU  - Dean DO
FAU - Bohn, M C
AU  - Bohn MC
LA  - eng
GR  - NEI ROI 05262/PHS HHS/United States
GR  - NINDS NS24279/NS/NINDS 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  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DNA, Complementary)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Astrocytes/*physiology
MH  - Brain-Derived Neurotrophic Factor
MH  - Cell Survival
MH  - Cells, Cultured
MH  - DNA, Complementary
MH  - Genetic Vectors
MH  - Nerve Growth Factors/metabolism
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Ganglion Cells/*physiology
MH  - Retroviridae
MH  - *Transfection
EDAT- 1994/05/30 00:00
MHDA- 2001/03/28 10:01
CRDT- 1994/05/30 00:00
PHST- 1994/05/30 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1994/05/30 00:00 [entrez]
AID - 0006-8993(94)91395-1 [pii]
AID - 10.1016/0006-8993(94)91395-1 [doi]
PST - ppublish
SO  - Brain Res. 1994 May 30;647(1):30-6. doi: 10.1016/0006-8993(94)91395-1.