Microglia/macrophages responses to kainate-induced injury in the rat retina.
The present study was aimed to elucidate how retinal microglia/macrophages would respond to neuronal death after intravitreal kainate injection. An increased expression of the complement receptor type 3 (CR3) and an induction of the major histocompatibility complex (MHC) class II and ED-1 antigens were mainly observed in the inner retina after kainate injection. Prominent cell death revealed by Fluoro Jade B (FJB) staining and ultrastructural examination appeared at the inner border of the inner nuclear layer (INL) at 1 day post-injection. Interestingly, some immunoreactive cells appeared at the outer segment of photoreceptor layer (OSPRL) at different time intervals. Our quantitative analysis further showed that CR3 immunoreactivity was drastically increased peaking at 7 days but subsided thereafter. MHC class II and ED-1 immunoreactivities showed a moderate but steady increase peaking at 3 days and declined thereafter. Double labeling study further revealed that retinal microglia/macrophages expressed concurrently CR3 and ED-1 antigens (OX-42+/ED-1+) or MHC class II molecules (OX-42+/OX-6+) and remained branched in shape at early stage of kainate challenge. By electron microscopy, microglia/macrophages with CR3 immunoreactivity displayed abundant cytoplasm containing a few vesicles and phagosomes. Other cells ultrastructurally similar to Müller cells or astrocytes could also engulf exogenous substances. In conclusion, retinal microglia/macrophages responded vigorously to kainate-induced neuronal cell death that may also trigger the recruitment of macrophages from neighboring tissues and induce the phagocytotic activity of cells other than retinal microglia/macrophages.
Chang
Min-Lin
ML
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1, Section 1, Jen Ai Road, Taipei 100, Taiwan.
Wu
Ching-Hsiang
CH
Chien
Hsiung-Fen
HF
Jiang-Shieh
Ya-Fen
YF
Shieh
Jeng-Yung
JY
Wen
Chen-Yuan
CY
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011951:Receptors, Complement / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000276:immunology* / Q000293:injuries
D018690:Excitatory Amino Acid Agonists; D000949:Histocompatibility Antigens Class II; D011951:Receptors, Complement; D007608:Kainic Acid