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However, the role of monocytes has yet to be fully investigated; therefore, we used <jats:italic>Ccr2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice to study the role of CCR2<jats:sup>+<\/jats:sup> inflammatory monocytes in the pathogenesis of diabetes-induced degeneration of retinal capillaries.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Experimental diabetes was induced in wild-type and <jats:italic>Ccr2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice using streptozotocin. After 2 months, superoxide levels, expression of inflammatory genes, leucostasis, leucocyte- and monocyte-mediated cytotoxicity against retinal endothelial cell death, retinal thickness and visual function were evaluated. Retinal capillary degeneration was determined after 8 months of diabetes. Flow cytometry of peripheral blood for differential expression of CCR2 in monocytes was assessed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In nondiabetic mice, CCR2 was highly expressed on monocytes, and <jats:italic>Ccr2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice lack CCR2<jats:sup>+<\/jats:sup> monocytes in the peripheral blood. Diabetes-induced retinal superoxide, expression of proinflammatory genes <jats:italic>Ino<\/jats:italic>s and <jats:italic>Icam1<\/jats:italic>, leucostasis and leucocyte-mediated cytotoxicity against retinal endothelial cells were inhibited in diabetic <jats:italic>Ccr2<\/jats:italic>-deficient mice and in chimeric mice lacking <jats:italic>Ccr2<\/jats:italic> only from myeloid cells. In order to focus on monocytes, these cells were immuno-isolated after 2 months of diabetes, and they significantly increased monocyte-mediated endothelial cell cytotoxicity ex vivo. Monocytes from <jats:italic>Ccr2<\/jats:italic>-deficient mice caused significantly less endothelial cell death. The diabetes-induced retinal capillary degeneration was inhibited in <jats:italic>Ccr2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice and in chimeric mice lacking <jats:italic>Ccr2<\/jats:italic> only from myeloid cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>CCR2<jats:sup>+<\/jats:sup> inflammatory monocytes contribute to the pathogenesis of early lesions of diabetic retinopathy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-022-05860-w","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T04:41:38Z","timestamp":1674708098000},"page":"590-602","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["CCR2-positive monocytes contribute to the pathogenesis of early diabetic retinopathy in mice"],"prefix":"10.1007","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-2147","authenticated-orcid":false,"given":"Aicha","family":"Saadane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"Veenstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Minns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Abubakr Elghazali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma M.","family":"Lessieur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pearlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy S.","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"issue":"1","key":"5860_CR1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S0002-9440(10)63952-1","volume":"158","author":"AM Joussen","year":"2001","unstructured":"Joussen AM, Murata T, Tsujikawa A, Kirchhof B, Bursell SE, Adamis AP (2001) Leukocyte-mediated endothelial cell injury and death in the diabetic retina. 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