Macrophages in the retina of normal Lewis rats and their dynamics after injection of lipopolysaccharide.

PURPOSE

To investigate the density, distribution, and morphology of macrophages (bone marrow-derived microglia) and major histocompatibility complex (MHC) class II-positive cells in the retina of Lewis rats and the dynamics of these cells after systemic lipopolysaccharide (LPS) injection.

METHODS

Immunohistochemistry was carried out using monoclonal antibodies specific to monocytes and macrophages (ED1, ED2) and MHC class II-positive cells (OX-6) on whole-mounts of the retina obtained from Lewis rats before and at different time points after footpad injection of 200 micrograms of LPS.

RESULTS

The inner layers of the normal retina contained a network of macrophages, whereby ED1 and ED2 staining revealed similar results. Macrophages were either dendritiform or pleiomorphic in morphology, with the former predominant. The density of positive cells was higher at the peripheral part and the periequatorial part (271 +/- 10 cells/mm2 and 267 +/- 9 cells/mm2, respectively) than at the posterior part (196 +/- 11 cells/mm2; P < 0.0001 in both cases). Lipopolysaccharide injection induced an early adherence of monocytes to retinal blood vessels, followed by a massive influx of the macrophages into the retina. The ED1-ED2 positive cells showed a variety of morphologic appearances: large round cells, pleiomorphic cells, and dendritiform cells. Pleiomorphic cells were striking at 48 hours, whereas dendritiform cells were predominant in the whole retina at 72 hours and thereafter. On day 14, the dendritiform cell numbers returned to approximately preinjection levels. Major histocompatibility class II-positive cells could not be found in the normal retina, nor after LPS injection.

CONCLUSIONS

The network of MHC class II-negative microglia 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 influx of macrophages into the retina. The absence of MHC class II-positive cells in the retina after LPS challenge may be an important protective mechanism against possible autoimmune damage.