The migratory potential of vitally labelled microglial cells within the retina of rats with hereditary photoreceptor dystrophy

Abstract

We employed a recently developed technique of labelling retinal microglial cells to identify these cells within the retinal parenchyma and to determine their role during degenerative diseases. In a first set of experiments we retrogradely labelled the ganglion cells from the superior colliculus of neonatal pups of the royal college of surgeons (RCS)-strain with the fluorescent dye 4Di-10ASP [N-4-4-(4-didecylaminostyryl-N-methylpropidium iodide)] at the day of birth. In a second group of young rats of the same strain retrograde staining of ganglion cells was performed by applying the fluorescent dye at the cross-sectional area of the transected optic nerve. In both experimental groups, prelabelled ganglion cells die. In the neonatal rats ganglion cells disappear because the initial neuronal cell population becomes naturally reduced by about 35% in the course of the programed cell death, which takes place during the first 2 weeks of life. In the mature rat, ganglion cells die as a consequence of the axotomy. In both cases, the fluorescent dye, which is a lipid inserted into the cell membrane, labels the ganglion cell bodies after retrograde transport from the axons. In the course of their degradation the dye is then selectively taken up by intraretinal microglial cells in the ganglion cell and inner plexiform layers. In both groups of experiments, fluorescently labelled microglial cells were redistributed from the inner retina toward the photoreceptor cell layer, which is afflicted by chronic photoreceptor dystrophy. Similar migration does not occur when the same experiments were repeated with non-dystrophic normal rats. The experimental results suggest that intraretinal microglial cells possess a migratory potential and make use of it when the cells are exposed to degeneration-induced stimuli, the nature of which remains to be characterized.