RGD Reference Report - Prolonged delivery of brain-derived neurotrophic factor by adenovirus-infected Muller cells temporarily rescues injured retinal ganglion cells. - Rat Genome Database

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Prolonged delivery of brain-derived neurotrophic factor by adenovirus-infected Muller cells temporarily rescues injured retinal ganglion cells.

Authors: Di Polo, A  Aigner, LJ  Dunn, RJ  Bray, GM  Aguayo, AJ 
Citation: Di Polo A, etal., Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3978-83.
RGD ID: 8655637
Pubmed: PMID:9520478   (View Abstract at PubMed)
PMCID: PMC19948   (View Article at PubMed Central)

In this study, we demonstrate that: (i) injection of an adenovirus (Ad) vector containing the brain-derived neurotrophic factor (BDNF) gene (Ad.BDNF) into the vitreous chamber of adult rats results in selective transgene expression by Muller cells; (ii) in vitro, Muller cells infected with Ad.BDNF secrete BDNF that enhances neuronal survival; (iii) in vivo, Ad-mediated expression of functional BDNF by Muller cells, temporarily extends the survival of axotomized retinal ganglion cells (RGCs); 16 days after axotomy, injured retinas treated with Ad.BDNF showed a 4.5-fold increase in surviving RGCs compared with control retinas; (iv) the transient expression of the BDNF transgene, which lasted approximately 10 days, can be prolonged with immunosuppression for at least 30 days, and such Ad-mediated BDNF remains biologically active, (v) persistent expression of BDNF by infected Muller cells does not further enhance the survival of injured RGCs, indicating that the effect of this neurotrophin on RGC survival is limited by changes induced by the lesion within 10-16 days after optic nerve transection rather than the availability of BDNF. Thus, Ad-transduced Muller cells are a novel pathway for sustained delivery of BDNF to acutely-injured RGCs. Because these cells span the entire thickness of the retina, Ad-mediated gene delivery to Muller cells may also be useful to influence photoreceptors and other retinal neurons.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Optic Nerve Injuries  ISOBdnf (Mus musculus)8655637; 8655637 RGD 
Optic Nerve Injuries  IDA 8655637 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bdnf  (brain-derived neurotrophic factor)

Genes (Mus musculus)
Bdnf  (brain derived neurotrophic factor)

Genes (Homo sapiens)
BDNF  (brain derived neurotrophic factor)


Additional Information