Short communication: protection of axotomized retinal ganglion cells by adenovirally delivered BDNF in vivo.
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.
Department of Neurology, University Hospital, D-72076 Tübingen, Germany. stefan.isenmann@tuebingen-mpg-de
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Isenmann
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Klöcker
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Gravel
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Bähr
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001370:Axonal Transport; D019771:Axotomy; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D017403:In Situ Hybridization; D007267:Injections; D009900:Optic Nerve / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D014162:Transfection
D001557:Benzenesulfonates; D019208:Brain-Derived Neurotrophic Factor; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D012333:RNA, Messenger; C094272:N-tert-butyl-(2-sulfophenyl)nitrone