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Protection of axotomized retinal ganglion cells by adenovirally delivered BDNF in vivo
Author(s) -
Isenmann Stefan,
Klöcker Nikolaj,
Gravel Claude,
Bähr Mathias
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00325.x
Subject(s) - in vivo , ganglion , neuroscience , retinal ganglion cell , retina , biology , microbiology and biotechnology , genetics
Following intraorbital transection of the optic nerve (ON) in rats, more than 80% of the retinal ganglion cell (RGC) population die by apoptosis within 14 days. Repeated intraocular injection of brain‐derived neurotrophic factor (BDNF) has been efficient in enhancing RGC survival following ON axotomy. The present study was designed to define a potential survival‐promoting effect of adenovirally administered BDNF on axotomized RGCs. A single injection of an adenoviral vector expressing the human BDNF gene from a CMV promoter/enhancer (Ad‐BDNF) enhanced RGC survival 14 days after axotomy by 40.3%. Moreover, a combinatory treatment regimen consisting of intraocular Ad‐BDNF administration and systemic application of the free radical scavenger, N‐tert‐butyl‐(2‐sulphophenyl)‐nitrone (S‐PBN), enhanced RGC survival by 63.0%. Our data demonstrate that adenoviral delivery of neurotrophic factors to the vitreous body is a feasible approach for the prevention of axotomy‐induced RGC death. Further, as shown for S‐PBN, therapeutic regimens that combine local virus‐mediated gene delivery with systemic administration of protective compounds, may offer promising strategies for future treatment also in human neurodegenerative conditions.