AXON-MEDIATED GENE-TRANSFER OF RETINAL GANGLION-CELLS IN-VIVO

Modification of the intracellular functions of mature neurons through specific gene transfer has many potential applications, Here we presen t a new methodology for the successful transfection of retinal ganglio n cells by administration of plasmid at the cut end of the optic nerve , or at their intact axon terminals; the latter is significantly more efficient. Plasmids contained either the SV40 promoter linked to the l uciferase gene, or the CMV or RSV promoter linked to the lacZ gene. As says for both reporter genes demonstrated significant expression of ex ogenous DNA in the retina for at least 10 days after retrograde transp ort, Duration of expression was extended to 20 days or more (duration of the experiment) when plasmid DNA was condensed with poly(L-lysine). beta-Galactosidase analysis revealed transfection of ganglion cells i n high numbers. Such an approach for gene delivery to specific subpopu lations of neurons might be useful in studies of molecular functions i n vivo and as an experimental therapeutic strategy to extend survival and restore their function. (C) 1997 John Wiley & Sons, Inc.