Microglia-Derived Nerve Growth Factor Causes Cell Death in the Developing Retina

While nerve growth factor (NGF) is best known for its trophic functions, recent experiments indicate that it can also cause cell death during development by activating the neurotrophin receptor p75. We now identify microglial cells as the source of NGF as a killing agent in the developing eye. When the retina is separated from the surrounding tissue before colonization by microglial cells, no NGF can be detected, and cell death is dramatically reduced. It is restored by the addition of microglial cells, an effect that is blocked by NGF antibodies. NGF adsorbed at the surface of beads, but not soluble NGF, mimics the killing action of microglial cells. These results indicate an active role for macrophages in neuronal death.