MICROGLIAL CELLS INVADE THE OUTER RETINA AS PHOTORECEPTORS DEGENERATEIN ROYAL-COLLEGE OF SURGEONS RATS

Purpose. Photoreceptor degeneration is accompanied by the invasion of phagocytic cells into the outer retina of Royal College of Surgeons (R CS) rats. Previous studies suggested that these mononuclear phagocytes were blood-borne macrophages and not retinal pigment epithelial cells nor Muller glia. Thus, immunospecific markers were used to identify t hese cells and to determine their distribution in the dystrophic retin a. Methods. Retinas from RCS and control (RCS-rdy(+)) rats were proces sed for immunocytochemistry using antibodies against phosphotyrosine, which labels both microglial cells and peripheral macrophages, and ED2 , which labels peripheral macrophages only. As a positive control to d emonstrate ED2-labeling of peripheral macrophages that enter the retin a during injury, experiments were performed using needle-punctured Lon g Evans rat retinas. Results. In normal animals, process-bearing, phos photyrosine-reactive cells were restricted to the inner retinal layers and the outer plexiform layer. In early dystrophic retinas, phosphoty rosine-reactive cells also were observed in the outer retinal layers. The number of phosphotyrosine-labeled cells in the outer retina increa sed substantially in later stages of dystrophy. ED2-reactive cells wer e observed in normal or dystrophic retinas only after needle puncture. Conclusions. These findings suggest that phagocytic cells during the early stages of dystrophy in RCS rat retinas are derived from resident microglial cells, not from peripheral macrophages. The migration of m icroglial cells into the outer retina when photoreceptor cells begin t o degenerate further suggests that they may play a major role in photo receptor cell death in the dystrophic retina.