Filamentous middle cerebral artery occlusion causes ischemic damage to the retina in mice

Background and Purpose - Filamentous middle cerebral artery occlusion (fMCAO) is the most frequently used focal cerebral ischemia model in rodents. The proximity of the ophthalmic artery to the middle cerebral artery suggests that fMCAO induces retinal ischemia. We therefore tested whether fMCAO induces ischemia/reperfusion damage in retina in mice. Methods - SV129EV mice were subjected to transient ( 30 or 60 minutes) fMCAO followed by reperfusion under isoflurane anesthesia. Retinal perfusion was evaluated by intravenous injection of fluorescent microspheres combined with fluorescent microscopy using flat-mounted retinas. The fluorescent density of ipsilateral retina relative to contralateral retina was determined in each animal. Retinal injury was assessed by cresyl violet staining and in situ TUNEL. Results - Microsphere analysis demonstrated perfusion defect in the ipsilateral retina after 60 minutes fMCAO and effective restoration after reperfusion. Thirty minutes fMCAO did not produce evident histological changes, even after 2 days of reperfusion. Sixty minutes fMCAO followed by 2 hours reperfusion resulted in extensive cell damage in the inner nuclear ( > 30%) and ganglion cell ( > 50%) layers. TUNEL demonstrated very few positive cells, suggesting that damaged cells were mainly undergoing nonapoptotic cell death. Conclusions - Sixty minutes fMCAO produces retinal injury in SV129EV mice. Potential visual dysfunction should be considered when a particular occlusion period is selected for studying neurological outcomes after fMCAO. Because visual disturbance is often associated with thrombotic/embolic stroke in humans, fMCAO represents an appropriate model for future studies aimed at understanding and ameliorating the changes that lead to retinal damage in these patients.