This research plan embraces the hypothesis that the visual system is dependent on specific neurotrophic factors for its development and maintenance and such factors play a central role in successful regenerative responses in this system. Therefore, our long-term objectives are to investigate how neurotrophic factors may influence mammalian retinal neurons during development and response to lesion. It is our belief that due to new technologies the mammalian visual system, treated both in a tissue culture and/or in vivo environment, now offers an excellent opportunity for the study of how these factors influence retinal neurons to develop and successfully regenerate. Consequently, we have recently developed successful fetal rat retinal explant and dissociated cell culture systems which exhibit neurite outgrowth. In this study we will take advantage of our recent finding that a new neurotrophic factor purified from pig brain stimulates fiber outgrowth from 18-19 day-old fetal rat retinal explants. This is the first time that a CNS derived neurotrophic factor has been isolated and in turn shown to stimulate embryonic mammalian CNS neurons and will be used as a theme for development in this proposal.
The specific aims of this proposal are: (1) to characterize in vitro and in vivo the new brain factor effects on the embryonic, neonatal and adult rat retina as well as in the visual centers of the brain and (2) to study the effects of the brain factor on retinal response to lesion in postnatal and adult rats. This proposed study will allow us for the first time to: (1) evaluate a new CNS derived neurotrophic factor in the developing mammalian CNS and (2) determine what effect this CNS derived factor has on recovery of the mammalian CNS from lesion which may have important application in understanding and attacking the problem of abortive regeneration in the optic nerve of man.
