PROTECTION OF AXOTOMIZED RETINAL GANGLION-CELLS BY ADENOVIRALLY DELIVERED BDNF IN-VIVO

Following intraorbital transection of the optic nerve (ON) in rats, mo re than 80% of the retinal ganglion cell (RGC) population die by apopt osis within 14 days. Repeated intraocular injection of brain-derived n eurotrophic factor (BDNF) has been efficient in enhancing RGC survival following ON axotomy. The present study was designed to define a pote ntial survival-promoting effect of adenovirally administered BDNF on a xotomized RGCs. A single injection of an adenoviral vector expressing the human BDNF gene from a CMV promoter/ enhancer (Ad-BDNF) enhanced R GC survival 14 days after axotomy by 40.3%. Moreover, a combinatory tr eatment regimen consisting of intraocular Ad-BDNF administration and s ystemic application of the free radical scavenger, N-tert-butyl-(2-sul phophenyl)-nitrone (S-PBN), enhanced RGC survival by 63.0%. Our data d emonstrate that adenoviral delivery of neurotrophic factors to the vit reous body is a feasible approach for the prevention of axotomy-induce d RGC death. Further, as shown for S-PBN, therapeutic regimens that co mbine local virus-mediated gene delivery with systemic administration of protective compounds, may offer promising strategies for future tre atment also in human neurodegenerative conditions.