. The differentiation of cell types and the formation of synaptic contacts within the neural retina are guided, in large part, by molecules in the extracellular environment. Trophic factors represent an important class of extrinsic signals and have been shown to regulate certain aspects of the differentiation, as well as the survival, of discrete neuronal populations elsewhere in the nervous system. Their actions in the developing retina are poorly understood at present. Progress in the cloning and identification of trophic factor families has begun to provide the tools with which to define their role in retinal cell differentiation. The proposed research focuses on the role of nerve growth factor (NGF) and related trophic factors in the formation of the chicken neural retina. Our recent work has shown that the embryonic and adult chicken retina synthesize NGF. We have proposed that it may act in a """"""""classical"""""""" manner as a target-derived factor for extrinsic neurons in the isthmo-optic nucleus (ION) that innervate the retina. However the embryonic retina also expresses a high level of NGF receptors, raising the possibility that NGF may act locally to regulate such early events as retina cell migration, differentiation and process outgrowth. A second factor structurally related to NGF, brain-derived trophic factor (BDNF), appears to act as a target-derived factor for retinal ganglion cells. This suggests that additional members of the NGF trophic factor family are likely to be important for guiding the normal development of the retina. The goals of this study are to first establish the relationship between the cell types that express NGF receptors and that synthesize NGF in the embryonic retina using presently available peptide antibody and nucleic acid probes. The role of NGF in retinal development will then be determined using antibodies to eliminate NGF in the embryonic eye at important development stages. The results will be interpreted with respect to two possible actions of NGF - 1) a target-derived factor regulating the survival of ION neurons and 2) a local regulator of retinal cell differentiation. Finally, chicken BDNF will be cloned and information about conserved sequences will be used to screen for additional members of the NGF/BDNF trophic factor family. The expression of BDNF and related trophic factors in the embryonic retina and optic tectum will be determined to assess their role in guiding retinal development. Defining the roles of NGF and related factors in the normal development of the retina will aid in the understanding of developmental and degenerative eye disorders and contribute to strategies and aimed at restoring retinal function following injury.
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