{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:33Z","timestamp":1787026593197,"version":"build-2736575974"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C3005694"],"award-info":[{"award-number":["2020R1A2C3005694"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Animal models of retinal artery occlusion (RAO) have been widely used in many studies. However, most of these studies prefer using a central retinal artery occlusion (CRAO) which is a typical global ischemia model of the retina, due to the technical limitation of producing single vessel targeted modeling with real-time imaging. A focal ischemia model, such as branch retinal artery occlusion (BRAO), is also needed for explaining interactions, including the immunological reaction between the ischemic retina and adjacent healthy retina. Accordingly, a relevant model for clinical RAO patients has been demanded to understand the pathophysiology of the RAO disease. Herein, we establish a convenient BRAO mouse model to research the focal reaction of the retina. As a photo-thrombotic agent, Rose bengal was intravenously injected into 7 week-old transgenic mice (CX3CR1-GFP) for making embolism occlusion, which causes pathology similarly to clinical cases. In an optimized condition, a 561 nm laser (13.1 mw) was projected to a targeted vessel to induce photo-thrombosis for 27 s by custom-built retinal confocal microscopy. Compared to previous BRAO models, the procedures of thrombosis generation were naturally and minimal invasively generated with real-time retinal imaging. In addition, by utilizing the self-remission characteristics of Rose bengal thrombus, a reflow of the BRAO with immunological reactions of the CX3CR1-GFP\n                    <jats:sup>+<\/jats:sup>\n                    inflammatory cells such as the retinal microglia and monocytes was monitored and analyzed. In this models, reperfusion began on day 3 after modeling. Simultaneously, the activation of CX3CR1-GFP\n                    <jats:sup>+<\/jats:sup>\n                    inflammatory cells, including the increase of activation marker and morphologic change, was confirmed by immunohistochemical (IHC) staining and quantitative real-time PCR. CD86 and Nox2 were prominently expressed on day 3 after the modeling. At day 7, blood flow was almost restored in the large vessels. CX3CR1-GFP\n                    <jats:sup>+<\/jats:sup>\n                    populations in both superficial and deep layers of the retina also increased around even in the BRAO peri-ischemic area. In summary, this study successfully establishes a reproducible BRAO modeling method with convenient capabilities of easily controllable time points and selection of a specific single vessel. It can be a useful tool to analyze the behavior of inflammatory cell after spontaneous arterial recanalization in BRAO and further investigate the pathophysiology of BRAO.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2022.897800","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:37:37Z","timestamp":1657845457000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Establishment of the reproducible branch retinal artery occlusion mouse model and intravital longitudinal imaging of the retinal CX3CR1-GFP+ cells after spontaneous arterial recanalization"],"prefix":"10.3389","volume":"9","author":[{"given":"Jehwi","family":"Jeon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunji","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee Myung","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Yong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyeop","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Me","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilhan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1167\/tvst.8.4.23","article-title":"Animal models used to simulate retinal artery occlusion: a comprehensive review.","volume":"8","author":"Vestergaard","year":"2019","journal-title":"Transl Vis Sci Technol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3389\/fncel.2018.00323","article-title":"Bidirectional microglia-neuron communication in health and disease.","volume":"12","author":"Szepesi","year":"2018","journal-title":"Front Cell Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1093\/ilar.44.2.85","article-title":"Animal models of focal and global cerebral ischemia.","volume":"44","author":"Traystman","year":"2003","journal-title":"ILAR J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"76","DOI":"10.14336\/AD.2014.050076","article-title":"Susceptibility to focal and global brain ischemia of Alzheimer mice displaying abeta deposits: effect of immunoglobulin.","volume":"5","author":"Heikkinen","year":"2014","journal-title":"Aging Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3171\/2014.9.JNS14778","article-title":"Consistent delayed unilateral neuronal death after modified transient focal cerebral ischemia in mice that mimics neuronal injury after transient global cerebral ischemia.","volume":"123","author":"Nishijima","year":"2015","journal-title":"J Neurosurg."},{"key":"B6","doi-asserted-by":"publisher","first-page":"8123","DOI":"10.1167\/iovs.11-8318","article-title":"Neuroprotection from retinal ischemia\/reperfusion injury by NOX2 NADPH oxidase deletion.","volume":"52","author":"Yokota","year":"2011","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"10659","DOI":"10.1073\/pnas.152321399","article-title":"Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury.","volume":"99","author":"Junk","year":"2002","journal-title":"Proc Natl Acad Sci USA."},{"key":"B8","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1038\/s41419-018-1044-5","article-title":"Rapamycin and fasting sustain autophagy response activated by ischemia\/reperfusion injury and promote retinal ganglion cell survival.","volume":"9","author":"Russo","year":"2018","journal-title":"Cell Death Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3727","DOI":"10.1167\/iovs.03-1324","article-title":"Heme oxygenase-1-related carbon monoxide and flavonoids in ischemic\/reperfused rat retina.","volume":"45","author":"Szabo","year":"2004","journal-title":"Invest Ophthalmol Vis Sci."},{"key":"B10","first-page":"1471","article-title":"Ischemia and reperfusion-induced histologic changes in the rat retina. 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