The rapid retrograde degeneration of neurons in the lateral geniculate nucleus (LGN) following damage to the visual cortex in adult mammals precludes subsequent axonal regeneration and restoration of function. In young animals of many species, LGN neurons also degenerate after damage to the visual cortex but, in contrast to adults, some neurons are spared and are able to establish new pathways resulting in remarkable behavioral compensation. Recent evidence suggests that basic fibroblast growth factor (bFGF) may prevent neuronal death. However, the lack of a suitable delivery system for administering trophic factors or their genes to non-dividing neurons has been a major obstacle in determining their efficacy in vivo. This Small Grant for Exploratory Research will permit the development of a Herpes simplex viral vector carrying the bFGF gene. This vector will be used to determine whether the production of bFGF in LGN neurons will prevent their degeneration after damage to the visual cortex in adult rat. These studies have the potential for improving the technology for gene therapy not only for treating damaged neurons in the visual system, but also neurons affected by damage, disease or genetic abnormality in any system in the mammalian brain or peripheral nervous system.
