Anatomical location of injected microglia in different activation states and time course of injury determines survival of retinal ganglion cells after optic nerve crush.

We show here that neuroprotection is not solely determined by the microglial activation state but factors such as the environment and time-course of the injury.Culture microglia can be treated in vitro and then injected in vivo.The cells migrate to the site of injury, cell body of retinal ganglion cells if in the vitreous or to the optic nerve if injected in the tail vein.Retinal ganglion cell death is dependent on the location the microglia act, time-course of injury, and activation state.Proinflammatory microglia can be neuroprotective early in the injury when the primary site of action is on the axons whereas hypoactivated microglia are neuroprotective early in injury when they act on the soma. Later in the injury, both become detrimental.