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Intravitreal injection of ranibizumab was performed 8\u2009weeks after diabetes onset. rMC-1 cells (rat M\u00fcller cell line) were treated with glyoxal for 24\u2009h with or without ranibizumab. The expression levels of inwardly rectifying K<jats:sup>+<\/jats:sup> channel 4.1 (Kir4.1), aquaporin 4 (AQP4), Dystrophin 71 (Dp71), VEGF-A, glutamine synthetase (GS) and sodium-potassium-ATPase (Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase) were examined using Western blot. VEGF-A in the supernatant of the cell culture was detected with ELISA. The intracellular potassium and sodium levels were detected with specific indicators.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared with normal control, protein expressions of Kir4.1 and AQP4 were down-regulated significantly in diabetic rat retinas, which were prevented by ranibizumab. The above changes were recapitulated in vitro. Similarly, the intracellular potassium level in glyoxal-treated rMC-1 cells was increased, while the intracellular sodium level and Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-ATPase protein level remained unchanged, compared with control. However, ranibizumab treatment decreased intracellular sodium, but not potassium.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Ranibizumab protected M\u00fcller cells from\u00a0diabetic intracellular edema through the up-regulation of Kir4.1 and AQP4 by directly binding VEGF-A. It also caused a reduction in intracellular osmotic pressure.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s40662-021-00237-3","type":"journal-article","created":{"date-parts":[[2021,4,17]],"date-time":"2021-04-17T14:02:50Z","timestamp":1618668170000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Anti-VEGF therapy prevents M\u00fcller intracellular edema by decreasing VEGF-A in diabetic retinopathy"],"prefix":"10.1186","volume":"8","author":[{"given":"Tianqin","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Tong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0601-4342","authenticated-orcid":false,"given":"Jingfa","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,17]]},"reference":[{"issue":"13","key":"237_CR1","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1056\/NEJMra1005073","volume":"366","author":"DA Antonetti","year":"2012","unstructured":"Antonetti DA, Klein R, Gardner TW. 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