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 (IRBP)-induced experimental autoimmune uveitis (EAU) we examined cellular reactions in the optic pathway (retina, choroid, optic nerve, optic tract, colliculus 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 immunohistochemistry with monoclonal antibodies against ED , ED2, OX6, OX22, EMAP II, AIF-1 and W3/13. In the retina, choroid and distal optic nerve increased immunoreactivity to ED1, OX6, OX22, EMAP II, AIF-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 expression 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 also seen in the distal optic nerve and optic tract. This remote microglial activation, however, differs in intensity, time course and expression of activation markers, thus indicating different activation cascades. The mild remote microglial activation is probably due to neuronal-microglial interactions resulting from neuronal damage in the retinal ganglion cell layer and nerve fiber layer with consecutive axonal degeneration and not from an inflammatory reaction as seen in the eye.
Fauser
S
S
Institute of Brain Research, University of Tuebingen, Germany.
Nguyen
T D
TD
Bekure
K
K
Schluesener
H J
HJ
Meyermann
R
R
D000818:Animals; D002831:Choroid Plexus / Q000473:pathology; D005136:Eye Proteins; D005260:Female; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000473:pathology; D017628:Microglia / Q000473:pathology*; D009900:Optic Nerve / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000473:pathology; D012177:Retinol-Binding Proteins / Q000378:metabolism*; D013477:Superior Colliculi / Q000473:pathology; D014605:Uveitis / Q000139:chemically induced* / Q000473:pathology*; D014793:Visual Cortex / Q000473:pathology; D000099214:Retinol-Binding Proteins, Interstitial
D005136:Eye Proteins; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial