Sick photoreceptors attract activated microglia from the ganglion cell layer: a model to study the inflammatory cascades in rats with inherited retinal dystrophy.
Understanding of neuron-glial interactions in neurodegenerative diseases remains limited, but is of crucial importance for unravelling the etiology of such disorders both in humans and in animals. The present work employed a new, function-dependent technique for examining the role of microglia in rats afflicted with inherited retinal photoreceptor degeneration (strain: royal college of surgeons, RCS). In this rat strain, which served as a surrogate for human inherited retinal photoreceptor dystrophy, the optic nerve was cut and the ganglion cells were retrogradely labelled with the fluorescent dye 4Di-10ASP. The experiment was performed under three different conditions: (1) at the 50th day of postnatal age (P50) when there is ongoing degeneration of photoreceptor cells, (2) at P110 when most photoreceptors were degenerated and (3) at P50 in non-dystrophic rats of the Sprague-Dawley strain. After axotomy-induced ganglion cell death and labelling of activated microglia by phagocytosis of the ganglion cell debris, this study monitored whether the labelled and therefore identifiable microglial cells within the severed ganglion cell layer (GCL) are prompted to migrate and to participate in phagocytosis of debris produced within the endogenously degenerating photoreceptor cell layer (PRL). Massive migration of microglial cells from the GCL to the PRL occurred in dystrophic animals with optic nerve transection at P50. Double-labelling of microglial cells with the fluorescent dye ingested within the GCL and with lipofuscin ingested within the PRL indicated the ability of these cells to perform double-phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Thanos
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Department of Ophthalmology, University of Tübingen, School of Medicine, FRG.
D000818:Animals; D001369:Axons / Q000502:physiology; D004195:Disease Models, Animal; D009410:Nerve Degeneration / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D010587:Phagocytosis / Q000502:physiology; D010786:Photoreceptor Cells / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000502:physiology*; D012173:Retinitis / Q000473:pathology* / Q000503:physiopathology