| First Author | Saadane A | Year | 2023 |
| Journal | Diabetologia | Volume | 66 |
| Issue | 3 | Pages | 590-602 |
| PubMed ID | 36698021 | Mgi Jnum | J:352217 |
| Mgi Id | MGI:7435516 | Doi | 10.1007/s00125-022-05860-w |
| Citation | Saadane A, et al. (2023) CCR2-positive monocytes contribute to the pathogenesis of early diabetic retinopathy in mice. Diabetologia 66(3):590-602 |
| abstractText | AIMS/HYPOTHESIS: Accumulating evidence suggests that leucocytes play a critical role in diabetes-induced vascular lesions and other abnormalities that characterise the early stages of diabetic retinopathy. However, the role of monocytes has yet to be fully investigated; therefore, we used Ccr2(-/-) mice to study the role of CCR2(+) inflammatory monocytes in the pathogenesis of diabetes-induced degeneration of retinal capillaries. METHODS: Experimental diabetes was induced in wild-type and Ccr2(-/-) 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. RESULTS: In nondiabetic mice, CCR2 was highly expressed on monocytes, and Ccr2(-/-) mice lack CCR2(+) monocytes in the peripheral blood. Diabetes-induced retinal superoxide, expression of proinflammatory genes Inos and Icam1, leucostasis and leucocyte-mediated cytotoxicity against retinal endothelial cells were inhibited in diabetic Ccr2-deficient mice and in chimeric mice lacking Ccr2 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 Ccr2-deficient mice caused significantly less endothelial cell death. The diabetes-induced retinal capillary degeneration was inhibited in Ccr2(-/-) mice and in chimeric mice lacking Ccr2 only from myeloid cells. CONCLUSIONS/INTERPRETATION: CCR2(+) inflammatory monocytes contribute to the pathogenesis of early lesions of diabetic retinopathy. |
