Cochlear gene transfer studies in animal models have utilized mainly two delivery methods: direct injection through the round window membrane (RWM) or intracochlear infusion through a cochleostomy. However, the surgical trauma, inflammation, and hearing loss associated with these methods lead us to investigate a less invasive delivery method. Herein, we studied the feasibility of a vector transgene-soaked gelatin sponge, Gelfoam, for transgene delivery into the mouse cochlea through an intact RWM. The Gelfoam absorbed with liposomes and adenovirus, but not with adeno-associated virus (AAV), was successful in mediating transgene expression across an intact RWM in a variety of cochlear tissues. The Gelfoam technique proved to be an easy, atraumatic, and effective, but vector-dependent, method of delivering transgenes through an intact RWM. Compared with the more invasive gene delivery methods, this technique represents a safer and a more clinically viable route of cochlear gene delivery in humans.
Otolaryngology-Head and Neck Surgery August T999 Conclusion: The findings suggest that FN may provide an important role in guiding cochlear neurons during the terminal innervation events of development. This expands on previous work (Woolf et al. Dev Brain Res 1992;65:21-33) that demonstrated the transient expression of FN beneath hair cells in the developing cochlea. It also appears that NT-3, but not GDNF, is involved in cochlear neurite pathfinding as well. Future investigations will focus on SG response to patterned arrangements of FN and other substrata components as well as to other stimulatory and inhibitory growth factors. Clinical Significance: These findings have implications in auditory neurite development and regeneration. Continued work in this arena will provide clues to enhancing the growth of inner ear neuronal processes. Such information may enhance techniques that promote neuronal growth and regeneration into cochlear prostheses.
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