Neurotrophic factors and their receptors in the developing avian retina and its tectal target

Abstract: Neurotrophic factors and their receptors are crucial for the formation of neuronal connections and for the neuronal survival during embryonic development of the nervous system. This has particularly been shown by studies of the PNS. The work of this thesis has aimed at clarifying where and when in the developing retina and its tectal target (as parts of the CNS), certain neurotrophic factors come into play. In a functional perspective, the focus has been on the possible involvement of these factors in the regulation of cell death / survival. Therefore, naturally occuring cell death in the developing avian retina was first studied. From the results, it is concluded that there is an early and a late phase of cell death in the developing retina. The cells dying during the early phase are proliferating retinal precursor cells, and the cells dying later are in the process of terminal differentiation. The timing and distribution of the dying cells suggest that the cell death is regulated. During retinal development two retinal cell types, amacrine cells and horizontal cells, express TrkA, a receptor for the neurotrophin nerve growth factor (NGF). These amacrine cells are shown to undergo cell death during the late cell death phase, but can be rescued by exogenous NGF. The horizontal cells in turn, are supported by NGF in an autocrine manner, and therefore survive. Two other neurotrophic factors brain-derived neurotrophic factor (BDNF) and glial cell-line derived neurotrophic factor (GDNF) are both expressed in the retina and in the target for retinal ganglion cells, the optic tectum. By the results, it is concluded that neuronal activity can regulate the expression of BDNF in the retina and optic tectum. Furthermore, GDNF can stimulate neurite outgrowth from retinal explants of a certain age. Taken together, the main result of this thesis is that neurotrophic factors indeed can work as autocrine survival factors in the developing CNS.