Many cells within the GCL expressed NT-3 both in vivo and in vitro, including RGCs, displaced amacrine cells, and glial cells. Localization of immunoreactivity was mainly within the nucleus and perinuclear cytoplasm, similar to that described in other species, including fish
21 and rat.
29 The function of NT-3 has been closely correlated with correct development, because it has been observed that antibodies that block NT-3 impair normal retinal development in chick embryos.
60 NT-3 promotes conversion of neuroepithelial cells into neurons during chicken retinal development
60 and facilitates the differentiation of retinal neurons in culture.
61 In addition, NT-3 promotes the survival of differentiated RGCs.
61 Responsiveness of differentiated RGCs to NT-3 occurs preferentially within a narrow period of retinal development, coincidental with the time that RGC axons reach their field of innervation. This developmental period also coincides with the time of maximal arborization and synapse formation within the retina.
61 Therefore, NT-3 has a role in central nervous system development that is distinct from and earlier than its role in promoting survival of differentiated neurons. It has been suggested that the two actions are probably exerted through two distinct types of NT-3 receptors, the first type appearing coincidentally with the main onset of retinal differentiation, the second type being expressed later when most retinal cells have already differentiated.
61 We also observed NT-3 immunoreactive fibers in the NFL. It has been demonstrated that astrocytes express and may secrete NT-3, which could stimulate oligodendrocyte proliferation in the optic nerve.
62 Recently, it has been demonstrated that NT-3 is produced by RGCs in chicken embryos and that some of this NT-3 is transported anterogradely to the optic tectum, possibly to regulate survival, synapse formation, or dendritic growth of tectal neurons. The p75 receptor is exported along RGC axons to the retinotectal terminals and may act as a carrier for NT-3.
63