Bax antisense oligonucleotides reduce axotomy-induced retinal ganglion cell death in vivo by reduction of Bax protein expression

Following transection of the optic nerve (ON), retinal ganglion cells (RGCs ) upregulate Bax protein expression and undergo apoptosis. The present stud y aimed at reducing Bax expression in order to test whether Bax plays a cau sative role in the induction of secondary RGC apoptosis. Following injectio n into the vitreous, fluoresceinated oligonucleotides transfected RGCs in v ivo at the injection site in the temporal superior retina. Following ON les ion, and repeated injections of a partially phosphorothioated Bax antisense oligonucleotide, but not following injection of control oligonucleotides, expression of Bax protein was locally inhibited, and the number of survivin g RGCs was increased in Bax antisense treated rats 8 days after axotomy, Ou r results indicate that Bax induction is a prerequisite for the execution o f RGC apoptosis following ON axotomy. While the Fax antisense strategy offe rs an exciting perspective to inhibit secondary neuronal degeneration in vi vo, both limited transfection efficacy, and the temporal restriction of thi s effect currently limit the use of this approach with respect to clinical applications for the treatment of neurodegeneration.