{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:44:31Z","timestamp":1790192671375,"version":"4.1.0"},"reference-count":48,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research","award":["18K09424"],"award-info":[{"award-number":["18K09424"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Background<\/jats:title>\n               <jats:p>Retinal ischemic stresses are associated with the pathogenesis of various retinal vascular diseases. To investigate pathological mechanisms of retinal ischemia, reproducible, robust and clinically significant experimental rodent models are highly needed. Previously, we established a stable murine model of chronic hypoperfusion retinal injuries by permanent unilateral common carotid artery occlusion (UCCAO) and demonstrated chronic pathological processes in the ischemic retina after the occlusion; however, retinal functional deficits and other acute retinal ischemic injuries by UCCAO still remain obscure. In this study, we attempted to examine retinal functional changes as well as acute retinal ischemic alterations such as retinal thinning, gliosis and cell death after UCCAO.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Methods<\/jats:title>\n               <jats:p>Adult mice (male C57BL\/6, 6\u20138 weeks old) were subjected to UCCAO in the right side, and retinal function was primarily measured using electroretinography for 14 days after the surgery. Furthermore, retinal thinning, gliosis and cell death were investigated using optical coherence tomography, immunohistochemistry and TUNEL assay, respectively.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>Functional deficits in the unilateral right retina started to be seen 7 days after the occlusion. Specifically, the amplitude of b-wave dramatically decreased while that of a-wave was slightly affected. 14 days after the occlusion, the amplitudes of both waves and oscillatory potentials were significantly detected decreased in the unilateral right retina. Even though a change in retinal thickness was not dramatically observed among all the eyes, retinal gliosis and cell death in the unilateral right retina were substantially observed after UCCAO.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusions<\/jats:title>\n               <jats:p>Along with previous retinal ischemic results in this model, UCCAO can stimulate retinal ischemia leading to functional, morphological and molecular changes in the retina. This model can be useful for the investigation of pathological mechanisms for human ischemic retinopathies and furthermore can be utilized to test new drugs for various ischemic ocular diseases.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.11665","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T07:40:44Z","timestamp":1624261244000},"page":"e11665","source":"Crossref","is-referenced-by-count":28,"title":["Retinal dysfunction induced in a mouse model of unilateral common carotid artery occlusion"],"prefix":"10.7717","volume":"9","author":[{"given":"Deokho","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heonuk","family":"Jeong","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukihiro","family":"Miwa","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan"},{"name":"Animal eye-care, Tokyo Animal Eye Clinic, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Shinojima","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusaku","family":"Katada","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Tsubota","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan"},{"name":"Tsubota Laboratory, Inc., Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"10.7717\/peerj.11665\/ref-1","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/0042-6989(68)90041-2","article-title":"The eclectroretinogram: its components and their origins","volume":"8","author":"Brown","year":"1968","journal-title":"Vision Research"},{"key":"10.7717\/peerj.11665\/ref-2","doi-asserted-by":"publisher","first-page":"e0194533","DOI":"10.1371\/journal.pone.0194533","article-title":"Risk of developing open-angle glaucoma in patients with carotid artery stenosis: a nationwide cohort study","volume":"13","author":"Chou","year":"2018","journal-title":"PLOS ONE"},{"issue":"3","key":"10.7717\/peerj.11665\/ref-3","doi-asserted-by":"publisher","first-page":"e0193961","DOI":"10.1371\/journal.pone.0193961","article-title":"Individual and temporal variability of the retina after chronic bilateral common carotid artery occlusion (BCCAO)","volume":"13","author":"Crespo-Garcia","year":"2018","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.11665\/ref-4","doi-asserted-by":"publisher","first-page":"28","DOI":"10.21037\/aes.2018.05.04","article-title":"Acute retinal arterial ischemia","volume":"3","author":"Dattilo","year":"2018","journal-title":"Annals of Eye Science"},{"key":"10.7717\/peerj.11665\/ref-5","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/S0006-8993(00)01937-5","article-title":"Chronic cerebral hypoperfusion: loss of pupillary reflex, visual impairment and retinal neurodegeneration","volume":"859","author":"Davidson","year":"2000","journal-title":"Brain Research"},{"key":"10.7717\/peerj.11665\/ref-6","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12933-020-01023-6","article-title":"The relationship between carotid disease and retinopathy in diabetes: a systematic review","volume":"19","author":"Drinkwater","year":"2020","journal-title":"Cardiovascular Diabetology"},{"key":"10.7717\/peerj.11665\/ref-7","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1177\/153857440604000301","article-title":"Current management of extracranial carotid artery disease","volume":"40","author":"Faries","year":"2006","journal-title":"Vasc Endovascular Surg"},{"key":"10.7717\/peerj.11665\/ref-8","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3389\/fphar.2020.00277","article-title":"Arginase pathway in acute retina and brain injury: therapeutic opportunities and unexplored avenues","volume":"11","author":"Fouda","year":"2020"},{"key":"10.7717\/peerj.11665\/ref-9","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1126\/science.1235294","article-title":"Emergence of individuality in genetically identical mice","volume":"340","author":"Freund","year":"2013","journal-title":"Science"},{"key":"10.7717\/peerj.11665\/ref-10","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1167\/iovs.03-1080","article-title":"Oscillatory potential analysis and ERGs of normal and diabetic rats","volume":"45","author":"Hancock","year":"2004","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"10.7717\/peerj.11665\/ref-11","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/s1350-9462(98)00037-8","article-title":"Progress in measurement of ocular blood flow and relevance to our understanding of glaucoma and age-related macular degeneration","volume":"18","author":"Harris","year":"1999","journal-title":"Progress in Retinal and Eye Research"},{"key":"10.7717\/peerj.11665\/ref-12","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1016\/0042-6989(85)90214-7","article-title":"Origin of the oscillatory potentials in the primate retina","volume":"25","author":"Heynen","year":"1985","journal-title":"Vision Research"},{"key":"10.7717\/peerj.11665\/ref-13","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.neuroscience.2008.06.038","article-title":"Neurodegeneration and cellular stress in the retina and optic nerve in rat cerebral ischemia and hypoperfusion models","volume":"155","author":"Kalesnykas","year":"2008","journal-title":"Neuroscience"},{"key":"10.7717\/peerj.11665\/ref-14","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1538\/expanim.60.481","article-title":"Effect of three types of mixed anesthetic agents alternate to ketamine in mice","volume":"60","author":"Kawai","year":"2011","journal-title":"Experimental Animals"},{"key":"10.7717\/peerj.11665\/ref-15","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1538\/expanim.18-0183","article-title":"Effects of an anesthetic mixture of medetomidine, midazolam, and butorphanol and antagonism by atipamezole in rabbits","volume":"68","author":"Kirihara","year":"2019","journal-title":"Experimental Animals"},{"key":"10.7717\/peerj.11665\/ref-16","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s10384-006-0326-0","article-title":"Changes of oscillatory potentials and photopic negative response in patients with early diabetic retinopathy","volume":"50","author":"Kizawa","year":"2006","journal-title":"Japanese Journal of Ophthalmology"},{"key":"10.7717\/peerj.11665\/ref-17","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.2337\/db07-1281","article-title":"Angiotensin II Type 1 receptor signaling contributes to synaptophysin degradation and neuronal dysfunction in the diabetic retina","volume":"57","author":"Kurihara","year":"2008","journal-title":"Diabetes"},{"key":"10.7717\/peerj.11665\/ref-18","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s00417-005-0006-7","article-title":"Chronic bilateral common carotid artery occlusion: a model for ocular ischemic syndrome in the rat","volume":"244","author":"Lavinsky","year":"2006","journal-title":"Graefe\u2019s Archive for Clinical and Experimental Ophthalmology"},{"key":"10.7717\/peerj.11665\/ref-19","doi-asserted-by":"publisher","first-page":"6045","DOI":"10.1096\/fj.201802144R","article-title":"Astrocytic cystine\/glutamate antiporter is a key regulator of erythropoietin expression in the ischemic retina","volume":"33","author":"Lee","year":"2019","journal-title":"FASEB Journal"},{"key":"10.7717\/peerj.11665\/ref-20","doi-asserted-by":"publisher","first-page":"108275","DOI":"10.1016\/j.exer.2020.108275","article-title":"A mouse model of retinal hypoperfusion injury induced by unilateral common carotid artery occlusion","volume":"201","author":"Lee","year":"2020","journal-title":"Experimental Eye Research"},{"key":"10.7717\/peerj.11665\/ref-21","doi-asserted-by":"publisher","first-page":"e61865","DOI":"10.3791\/61865","article-title":"A murine model of ischemic retinal injury induced by transient bilateral common carotid artery occlusion","volume":"1","author":"Lee","year":"2020","journal-title":"JoVE"},{"issue":"3","key":"10.7717\/peerj.11665\/ref-22","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3390\/ph14030223","article-title":"Fenofibrate protects against retinal dysfunction in a murine model of common carotid artery occlusion-induced ocular ischemia","volume":"14","author":"Lee","year":"2021","journal-title":"Pharmaceuticals"},{"key":"10.7717\/peerj.11665\/ref-23","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1006\/exer.2002.1170","article-title":"Early retinal damage in experimental diabetes: electroretinographical and morphological observations","volume":"74","author":"Li","year":"2002","journal-title":"Experimental Eye Research"},{"key":"10.7717\/peerj.11665\/ref-24","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s00417-019-04580-z","article-title":"SIRT1 is required for the neuroprotection of resveratrol on retinal ganglion cells after retinal ischemia-reperfusion injury in mice","volume":"258","author":"Luo","year":"2020","journal-title":"Graefe\u2019s Archive for Clinical and Experimental Ophthalmology"},{"key":"10.7717\/peerj.11665\/ref-25","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1007\/s12975-020-00799-9","article-title":"Relation of retinal oxygen measures to electrophysiology and survival indicators after permanent","volume":"11","author":"Matei","year":"2020","journal-title":"Translational Stroke Research"},{"key":"10.7717\/peerj.11665\/ref-26","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1152\/jn.1970.33.3.323","article-title":"Intracellular responses of the M\u00fcller (glial) cells of mudpuppy retina: their relation to b-wave of the electroretinogram","volume":"33","author":"Miller","year":"1970","journal-title":"Journal of Neurophysiology"},{"key":"10.7717\/peerj.11665\/ref-27","doi-asserted-by":"publisher","first-page":"75","DOI":"10.3389\/fneur.2012.00075","article-title":"Preclinical models to investigate retinal ischemia: advances and drawbacks","volume":"3","author":"Minhas","year":"2012","journal-title":"Frontiers in Neurology"},{"key":"10.7717\/peerj.11665\/ref-28","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.neuint.2019.03.008","article-title":"Pharmacological HIF inhibition prevents retinal neovascularization with improved visual function in a murine oxygen-induced retinopathy model","volume":"128","author":"Miwa","year":"2019","journal-title":"Neurochemistry International"},{"key":"10.7717\/peerj.11665\/ref-29","first-page":"645","article-title":"Effect of midazolam, medetomidine, and butorphanol tartrate combination anesthetic on electroretinograms of mice","volume":"25","author":"Miwa","year":"2019","journal-title":"Molecular Vision"},{"key":"10.7717\/peerj.11665\/ref-30","doi-asserted-by":"publisher","first-page":"9710","DOI":"10.1167\/iovs.11-8160","article-title":"Ligation of the pterygopalatine and external carotid arteries induces ischemic damage in the murine retina","volume":"52","author":"Ogishima","year":"2011","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"10.7717\/peerj.11665\/ref-31","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.preteyeres.2003.12.001","article-title":"Retinal ischemia: mechanisms of damage and potential therapeutic strategies","volume":"23","author":"Osborne","year":"2004","journal-title":"Progress in Retinal and Eye Research"},{"key":"10.7717\/peerj.11665\/ref-32","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/s41598-018-36400-5","article-title":"Functional and morphologic study of retinal hypoperfusion injury induced by bilateral common carotid artery occlusion in rats","volume":"9","author":"Qin","year":"2019","journal-title":"Scientific Reports"},{"key":"10.7717\/peerj.11665\/ref-33","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1113\/jphysiol.2002.030304","article-title":"Rod and cone contributions to the a-wave of the electroretinogram of the macaque","volume":"547","author":"Robson","year":"2003","journal-title":"The Journal of Physiology"},{"key":"10.7717\/peerj.11665\/ref-34","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/s1350-9462(97)00005-0","article-title":"Electrical responses from diabetic retina","volume":"17","author":"Shirao","year":"1998","journal-title":"Progress in Retinal and Eye Research"},{"key":"10.7717\/peerj.11665\/ref-35","doi-asserted-by":"publisher","first-page":"2353","DOI":"10.1167\/iovs.12-11103","article-title":"The effects of macular ischemia on visual acuity in diabetic retinopathy","volume":"54","author":"Sim","year":"2013","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"10.7717\/peerj.11665\/ref-36","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1111\/j.1745-7254.2008.00822.x","article-title":"Edaravone (MCI-186), a free radical scavenger, attenuates retinal ischemia\/reperfusion injury in rats","volume":"29","author":"Song","year":"2008","journal-title":"Acta Pharmaceutica Sinica"},{"key":"10.7717\/peerj.11665\/ref-37","first-page":"705","article-title":"Differences of brain pathological changes and cognitive function after bilateral common carotid artery occlusion between Sprague-Dawley and Wistar rats","volume":"71","author":"Sun","year":"2019","journal-title":"Acta Physiologica Sinica"},{"key":"10.7717\/peerj.11665\/ref-38","doi-asserted-by":"publisher","first-page":"RA138","DOI":"10.12659\/msm.883260","article-title":"Ocular ischemic syndrome - a systematic review","volume":"18","author":"Terelak-Borys","year":"2012","journal-title":"Medical Science Monitor: International Medical Journal of Experimental and Clinical Research"},{"key":"10.7717\/peerj.11665\/ref-39","doi-asserted-by":"publisher","first-page":"6243","DOI":"10.3390\/ijms21176243","article-title":"Pemafibrate protects against retinal dysfunction in a murine model of diabetic retinopathy","volume":"21","author":"Tomita","year":"2020","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.11665\/ref-40","doi-asserted-by":"publisher","first-page":"5878","DOI":"10.3390\/ijms20235878","article-title":"Pemafibrate prevents retinal pathological neovascularization by increasing FGF21 level in a murine oxygen-induced retinopathy model","volume":"20","author":"Tomita","year":"2019","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.11665\/ref-41","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/nrg3243","article-title":"The continuing value of twin studies in the omics era","volume":"13","author":"Van\u00a0Dongen","year":"2012","journal-title":"Nature Reviews Genetics"},{"key":"10.7717\/peerj.11665\/ref-42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.preteyeres.2015.06.003","article-title":"Glia-neuron interactions in the mammalian retina","volume":"51","author":"Vecino","year":"2016","journal-title":"Progress in Retinal and Eye Research"},{"key":"10.7717\/peerj.11665\/ref-43","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.expneurol.2015.05.006","article-title":"Models and mechanisms of vascular dementia","volume":"272","author":"Venkat","year":"2015","journal-title":"Experimental Neurology"},{"key":"10.7717\/peerj.11665\/ref-44","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/s1350-9462(98)00006-8","article-title":"Oscillatory potentials in the retina: what do they reveal","volume":"17","author":"Wachtmeister","year":"1998","journal-title":"Progress in Retinal and Eye Research"},{"key":"10.7717\/peerj.11665\/ref-45","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/S0006-8993(00)02216-2","article-title":"A comparison of strain-related susceptibility in two murine recovery models of global cerebral ischemia","volume":"868","author":"Wellons\u00a0Iii","year":"2000","journal-title":"Brain Research"},{"key":"10.7717\/peerj.11665\/ref-46","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1016\/j.exer.2005.09.019","article-title":"Complex neurodegeneration in retina following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats","volume":"82","author":"Yamamoto","year":"2006","journal-title":"Experimental Eye Research"},{"key":"10.7717\/peerj.11665\/ref-47","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S0006-8993(96)01453-9","article-title":"C57BL\/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in the murine transient forebrain ischemia","volume":"752","author":"Yang","year":"1997","journal-title":"Brain Research"},{"key":"10.7717\/peerj.11665\/ref-48","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/bf00207350","article-title":"New approaches to ophthalmic electrodiagnosis by retinal oscillatory potential, drug-induced responses from retinal pigment epithelium and cone potential","volume":"48","author":"Yonemura","year":"1979","journal-title":"Documenta Ophthalmologica"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/11665.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/11665.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/11665.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/11665.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T07:40:53Z","timestamp":1624261253000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/11665"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,21]]},"references-count":48,"alternative-id":["10.7717\/peerj.11665"],"URL":"https:\/\/doi.org\/10.7717\/peerj.11665","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,21]]},"article-number":"e11665"}}