The overall objective of this project is to investigate the failure of central nervous system (CNS) regneration in mammals, with particular emphasis on the retina and optic nerve. An understanding of this mechanism will facilitate the search for neuroregenerative agents. The project in its present phase involves comparative studies of the normal state as well as the reaction of optic axons to lesions, at various developmental ages and in various species (regenerating and non-regenerating). The techniques include specific stains for optic and glial fibers, and extracellular matrix at the light and electron microscopic levels. We also plan to utilize a new sucrose-osmotic technique we have developed for assaying intercellular adhesivity, using transmission electron microscopy. We will use this method to explore the hypothesis that adverse changes in cell adhesivity are largely responsible for regenerative failure.