Differential activation of microglial cells in local and remote areas of IRBP1169-1191-induced rat uveitis

Using a Lewis rat model of interphotoreceptor retinoid binding protein (IRB P)-induced experimental autoimmune uveitis (EAU) we examined cellular react ions in the optic pathway (retina, choroid, optic nerve, optic tract, colli culus superior, and visual cortex). Two to six animals were studied at days 0, 7, 9, 11, 12, 13, 14, 18 and 22 after immunization by immunohistochemis try with monoclonal antibodies against EDI, ED2, OX6, OX22, EMAP II, AIF-1 and W3/13. In the retina, choroid and distal optic nerve increased immunore activity to EDI, OX6, OX22, EMAP II, ArF-1 and W3/13 was initially observed at day 9, peaked at days 13-14 and diminished rapidly from day 18 onwards. No changes were seen in the density of ED2-positive resident macrophages. In the optic tract, ED1 and OX6 expression was induced in microglial cells beginning with day 11 and persisted until day 22. AIF-1, EMAP II and ED2 ex pression was not visibly up-regulated and no lymphocytic infiltrates (OX22- , W3/13-positive cells) were observed. In the central projection fields, no cellular reaction could be found. Thus, cellular response in IRBP-induced rat uveoretinitis is not restricted to the eye. Microglial activation is al so seen in the distal optic nerve and optic tract. This remote microglial a ctivation, however, differs in intensity, time course and expression of act ivation markers, thus indicating different activation cascades. The mild re mote microglial activation is probably due to neuronal-microglial interacti ons resulting from neuronal damage in the retinal ganglion cell layer and n erve fiber layer with consecutive axonal degeneration and not from an infla mmatory reaction as seen in the eye.