MACROPHAGES IN THE RETINA OF NORMAL LEWIS RATS AND THEIR DYNAMICS AFTER INJECTION OF LIPOPOLYSACCHARIDE

Purpose. To investigate the density, distribution, and morphology of m acrophages (bone marrow-derived microglia) and major histocompatibilit y complex (MHC) class II-positive cells in the retina of Lewis rats an d the dynamics of these cells after systemic lipopolysaccharide (LPS) injection. Methods. Immunohistochemistry was carried out using monoclo nal antibodies specific to monocytes and macrophages (ED1, ED2) and MH C class II-positive cells (OX-6) on whole-mounts of the retina obtaine d from Lewis rats before and at different time points after footpad in jection of 200 mu g of LPS. Results. The inner layers of the normal re tina contained a network of macrophages, whereby ED1 and ED2 staining revealed similar results. Macrophages were either dendritiform or plei omorphic in morphology, with the former predominant. The density of po sitive cells was higher at the peripheral part and the periequatorial part (271 +/- 10 cells/mm(2) and 267 +/- 9 cells/mm(2), respectively) than at the posterior part (196 +/- 11 cells/mm2; P < 0.0001 in both c ases). Lipopolysaccharide injection induced an early adherence of mono cytes to retinal blood vessels, followed by a massive influx of the ma crophages into the retina. The ED1-ED2 positive cells showed a variety of morphologic appearances: large round cells, pleiomorphic cells, an d dendritiform cells. Pleiomorphic cells were striking at 48 hours, wh ereas dendritiform cells were predominant in the whole retina at 72 ho urs and thereafter. On day 14, the dendritiform cell numbers returned to approximately preinjection levels. Major histocompatibility class I I-positive cells could not be found in the normal retina, nor after LP S injection. Conclusions. The network of MHC class II-negative microgl ia in the retina were studied. These cells may play an important role in immunoregulation and stability of the immunologic microenvironment within the retina. Systemic LPS injection was followed by a massive in flux of macrophages into the retina. The absence of MHC class II-posit ive cells in the retina after LPS challenge may be an important protec tive mechanism against possible autoimmune damage.