title: Severity of middle cerebral artery occlusion determines retinal deficits in rats.
abstract: Middle cerebral artery occlusion (MCAO) using the intraluminal suture technique is a common model used to study cerebral ischemia in rodents. Due to the proximity of the ophthalmic artery to the middle cerebral artery, MCAO blocks both arteries, causing both cerebral ischemia and retinal ischemia. While previous studies have shown retinal dysfunction at 48h post-MCAO, we investigated whether these retinal function deficits persist until 9days and whether they correlate with central neurological deficits. Rats received 90min of transient MCAO followed by electroretinography at 2 and 9days to assess retinal function. Retinal damage was assessed with cresyl violet staining, immunohistochemistry for glial fibrillary acidic protein (GFAP) and glutamine synthetase, and TUNEL staining. Rats showed behavioral deficits as assessed with neuroscore that correlated with cerebral infarct size and retinal function at 2days. Two days after surgery, rats with moderate MCAO (neuroscore <5) exhibited delays in electroretinogram implicit time, while rats with severe MCAO (neuroscore ≥5) exhibited reductions in amplitude. Glutamine synthetase was upregulated in Müller cells 3days after MCAO in both severe and moderate animals; however, retinal ganglion cell death was only observed in MCAO retinas from severe animals. By 9days after MCAO, both glutamine synthetase labeling and electroretinograms had returned to normal levels in moderate animals. Early retinal function deficits correlated with behavioral deficits. However, retinal function decreases were transient, and selective retinal cell loss was observed only with severe ischemia, suggesting that the retina is less susceptible to MCAO than the brain. Temporary retinal deficits caused by MCAO are likely due to ischemia-induced increases in extracellular glutamate that impair signal conduction, but resolve by 9days after MCAO.
authors: Emergency Medicine, Emory University, Atlanta, GA 30322, USA; Ophthalmology, Emory University, Atlanta, GA 30322, USA. Electronic address: restewa@emory.edu.
authors: Rachael S
authors: RS
authors: Allen
authors: Emergency Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: isayeed@emory.edu.
authors: Iqbal
authors: I
authors: Sayeed
authors: Emergency Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: hcale@u.washington.edu.
authors: Heather A
authors: HA
authors: Cale
authors: Emergency Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: cillakat@gmail.com.
authors: Katherine C
authors: KC
authors: Morrison
authors: Ophthalmology, Emory University, Atlanta, GA 30322, USA. Electronic address: jboatri@emory.edu.
authors: Jeffrey H
authors: JH
authors: Boatright
authors: Ophthalmology, Emory University, Atlanta, GA 30322, USA; Rehab R&D Center of Excellence, Atlanta VA Medical Center, Decatur, GA 30033, USA. Electronic address: mpardue@emory.edu.
authors: Machelle T
authors: MT
authors: Pardue
authors: Emergency Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: donald.stein@emory.edu.
authors: Donald G
authors: DG
authors: Stein
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism; D004596:Electroretinography; D005110:Extracellular Space / Q000378:metabolism; D005123:Eye / Q000098:blood supply; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000209:etiology* / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase
keywords: Electroretinogram; Focal ischemia; Middle cerebral artery occlusion; Rat; Retina; Retinal ischemia