{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:04:08Z","timestamp":1791389048799,"version":"4.3.3"},"reference-count":124,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Central retinal vein occlusion (CRVO) causes macular edema and subsequent vision loss and is common in people with diseases such as arteriosclerosis and hypertension. Various treatments for CRVO-associated macular edema have been trialed, including laser photocoagulation, with unsatisfactory results. However, when the important pathogenic role of vascular endothelial growth factor (VEGF) in macular edema was identified, the treatment of CRVO was revolutionized by anti-VEGF therapy. However, despite the success of intraocular injection of anti-VEGF agents in many patients with CRVO, some patients continue to suffer from refractory or recurring edema. In addition, the expression of inflammatory cytokines increases over time, causing more severe inflammation and a condition that is increasingly resistant to anti-VEGF therapy. This indicates that the pathogenesis of macular edema in CRVO is more complex than originally thought and may involve factors or cytokines associated with inflammation and ischemia other than VEGF. CRVO is also associated with leukocyte abnormalities and a gradual reduction in retinal blood flow velocity, which increase the likelihood of it developing from the nonischemic type into the more severe ischemic type; in turn, this results in excessive VEGF expression and subsequent neovascular glaucoma. Here, we review the role of different factors and cytokines involved in CRVO pathogenesis and propose a mechanism that holds promise for the development of novel therapies.<\/jats:p>","DOI":"10.3390\/jcm9113457","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T21:21:00Z","timestamp":1604006460000},"page":"3457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Cytokines and Pathogenesis of Central Retinal Vein Occlusion"],"prefix":"10.3390","volume":"9","author":[{"given":"Hidetaka","family":"Noma","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Shimura","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo 193-0998, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.ophtha.2006.11.011","article-title":"Interventions for central retinal vein occlusion: An evidence-based systematic review","volume":"114","author":"Mohamed","year":"2007","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.ophtha.2010.02.022","article-title":"Ranibizumab for macular edema following central retinal vein occlusion: Six-month primary end point results of a phase III study","volume":"117","author":"Brown","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_3","first-page":"5185128","article-title":"Cytokines and the Pathogenesis of Macular Edema in Branch Retinal Vein Occlusion","volume":"2","author":"Noma","year":"2019","journal-title":"J. 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