Nerve growth factor is expressed by postmitotic avian retinal horizontal cells and supports their survival during development in an autocrine mode ofaction

Cell death in the developing retina is regulated, but so far little is know n about what factors regulate the cell death. Several neurotrophic factors and receptors, including the neurotrophins and Trk receptors, are expressed during the critical time. We have studied the developing avian retina with respect to the role of nerve growth factor (NGF) in these processes. Our s tarting point for the work was that NGF and its receptor TrkA are expressed in a partially overlapping pattern in the inner nuclear layer of the devel oping retina. Our results show that TrkA and NGF-expressing cells are postm itotic, The first NGF-expressing cells were found on the vitreal side of th e central region of E5.5-E6 retina. This pattern changed and NGF-expressing cells identified as horizontal cells were later confined to the external i nner nuclear layer. We show that these horizontal cells co-express TrkA and NGF, unlike a subpopulation of amacrine cells that only expresses TrkA, In contrast to the horizontal cells, which survive, the majority of the TrkA- expressing amacrine cells die during a period of cell death in the inner nu clear layer. Intraocular injections of NGF protein rescued the dying amacri ne cells and injection of antisense oligonucleotides for NGF that block its synthesis, caused death among the TrkA-expressing horizontal cells, which normally would survive. Our results suggest that NGF supports the survival of TrkA expressing avian horizontal cells in an autocrine mode of action in the retina of E10-E12 chicks. The cells co-express TrkA and NGF and the ro le for NGF is to maintain the TrkA-expressing horizontal cells. The TrkA-ex pressing amacrine cells are not supported by NGF and subsequently die. In a ddition to the effect on survival, our results suggest that NGF plays a rol e in horizontal cell plasticity.