Fetal retina transplanted to the midbrain region of a newborn or adult rat survives, differentiates and forms connections with appropriate visual nuclei in the host brain. The project proposed here will examine further the development of retinal transplants in order to gain more insight into mechanisms active during development of normal retinal as well as further assess the potential for the use of retinal transplants as a clinical technique. This project has three major parts. First will be to evaluate possible mechanisms by which axons from retinal transplants find the appropriate visual nuclei. Particular attention will be given to the possibilities that transplant axons may initially be broadly distributed and then selectively retain only appropriate projections, that transplants axons may only follow host optic axons, or that transplant axons may preferentially tend to grow along the surface of the brain. This will involve using neuroanatomical techniques to study the developing projection of retinal transplants in normal and anophthalmic rats and transplants placed in various locations in the host brain. Second will be to determine if transplants of fetal retina made to the orbit can survive and form connections with the host brain. Third will be to evaluate the role of glia in directing the migration of neuroblasts in the developing retinal transplants. This will involve using immunohistochemical techniques with antibodies specific for retinal glia to identify the origin and distribution of glial cells in the developing transplants and to attempt to produce retinal transplants devoid of glia. This project will provide a greater understanding of mechanisms active in the devlopment of the normal visual system. With this understanding we can begin to construct the parameters required for using retinal transplants as a therapeutic means for treating retinal blindness.