Complex neurodegeneration in retina following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats.
Bilateral common carotid artery occlusion (BCCAO) produces moderate levels of ischemia in the retina of rats, which may simulate the inflow disturbances in severe carotid artery disease. ERG changes following acute BCCAO have been well described, but the effects of chronic BCCAO on the histopathology of the retina remain to be characterized in a reproducible model. Chronic BCCAO was induced in halothane-anaesthetized male Wistar rats and the retina fixed after 3, 6, or 24 hr, 1 week, and 2, 4, or 6 months. Cell counts and measurements of retinal layers were performed in H&E stained paraffin sections. Immunohistochemistry with a panel of fourteen antibodies served to examine the survival of different retinal cell class, astrocytic reactions and the expression of acute stress response proteins. A lectin method was used to label activated microglial cells. Microglial activation, heme oxygenase-1 upregulation and caspase-3 cleavage occurred during the first 24hr in the absence of overt cell death of retinal ganglion cells (RGC). Three waves of neurodegeneration followed. RGCs were affected after 1 week, followed by neurons in the inner nuclear layer at 2 months, and finally photoreceptors at 4 months. Immunomarkers indicated acute damage to horizontal cells and prolonged survival of amacrine cells. In conclusion, chronic BCCAO produced delayed neuronal death in the retina of adult male Wistar rats. The window of moderate changes of at least 1 day may facilitate molecular studies on retinal ganglion cell loss.
Yamamoto
Hideo
H
Bascom Palmer Eye Institute, Ophthalmic Biophysics Center, University of Miami School of Medicine, P.O. Box 016880, Miami, FL 33101, USA.
Schmidt-Kastner
Rainald
R
Hamasaki
Duco I
DI
Yamamoto
Hiroko
H
Parel
Jean-Marie
JM
D000818:Animals; D017536:Carotid Artery, Common; D016893:Carotid Stenosis / Q000150:complications*; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D007124:Immunoenzyme Techniques; D007511:Ischemia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012162:Retinal Degeneration / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D012171:Retinal Vessels