In adult mammals, severed optic axons, like most long projecting CNS axons, do not normally regenerate with the CNS so that axonal damage such as following spinal cord injury results in permanent deficits. However, it has recently been shown that optic fibers will regenerate when retina is placed in culture and that this regeneration is dramatically accelerated by prior optic nerve damage (Meyer & Miotke, 1987). This proposal will use such retinal explants from adult mice as a model to study the regenerative response of retinal fibers and to investigate cellular interactions and other factors that may be responsible for the lack of regeneration in the CNS. There are three major aims. The first is to optimize the culture conditions. Different gas mixtures, media, serum concentrations, additives, and methods of maintaining the explants will be explored. In addition, an attempt will be made to develop serum free culture conditions. The second aim will be to further characterize the regenerative response. The number of ganglion cells that survive at short and long culture periods will be counted. The effect of the time and position of the nerve injury prior to explanation will be explored. Elongation rate and growth distance will be measured for early and late explants. And the effect of explant size and shape will be explored. The third aim is to confront growing optic neurites with several conditions that may be relevant to their environment. These include pieces of optic nerve from adults or neonates, pieces of sciatic nerve and different substrates of extracellular matrix including laminin, collagen, and fibronectin.