Microglial responses in the avascular quail retina following transection of the optic nerve

Abstract

This study was undertaken to investigate microglial responses in the avascular central nervous system using the quail retina that is known to be devoid of blood vessels. Following intraorbital optic nerve transection (ONT), the quail retina was examined immunohistochemically at various times up to 6 months. A few days after transection, microglia in the inner retinal layers revealed features of activation. Activated cells displayed an amoeboid shape and enhanced QH1-immunoreactivity. The numbers of these amoeboid cells were rapidly increased, first in the inner plexiform layer (IPL), and then in the ganglion cell/nerve fiber layer (GCL/NFL) of the retina where retrograde degenerating ganglion cell processes and perikarya were located. By 6 months after transection, microglia regained their resting morphology, and their cell counts returned to control levels. At early time points of microglial activation, numerous QH1+ amoeboid cells were observed along the vitreal surface of the pecten and retinal region adjacent to the insertion of the pecten, where some amoeboid cells were attached underneath the internal limiting membrane, and appeared to squeeze through the optic nerve fiber bundles. A considerable number of these amoeboid cells in the GCL/NFL and the IPL were labeled with PCNA, suggesting that active exogenous migration (from the pecten) and in situ proliferation of precursor cells contribute to the increase in microglial population of the degenerating retina. On the other hand, TUNEL-positive microglia appeared in the GCL/NFL at later time points indicate that the decrease of microglial numbers is in part due to apoptosis in these layers. Although some aspects of microglial activation in the avascular retina appear unique, their consequences were similar to those described in vascular retinae of mammals, a finding indicates that blood vessels are not a prerequisite for microglial activation, and microglial precursors could migrate long distance to reach the lesioned site, which is not accessible via blood vessels. Our data provide the first analysis of microglial activation in the avascular central nervous system (CNS), and suggest that the quail retina is a useful model for studies of microglial behavior in CNS.