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A. M. Serra, J. M. Waddell, M. A. Cotter, H. Xu, J. V. Forrester; Entrapment of CD11b Positive Monocyte in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4986.
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Inflammation might play a role in the development of diabetic retinopathy (DR). Monocytes/macrophages have been implicated in the initiation of microvascular damage in diabetes. In addition, leukocytes from diabetes have been shown to have increased expression of adhesion molecules and greater adhesion to endothelial cells. The aim of this study was to determine whether increased expression of adhesion molecules and/or their ligands was restricted to any specific leukocyte subtype.
Diabetes was induced in C57BL/6 mice by intraperitoneal injection of streptozotocin (STZ). Adhesion molecule expression in the retina and leukocyte subsets was analysed 2 weeks later. Immunofluorescence staining was performed in retinal wholemounts of normal and diabetic induced mice and observed by confocal laser scanning microscopy (LSM510 META). Intravascular entrapped leukocytes were counted by a fluorescence microscopy. In addition, retinal cell suspension prepared by collagenase/dispase digestion and isolated blood leukocytes were analysed by flow cytometry using antibodies to PECAM-1, ICAM-1, VCAM-1 and CD62P for endothelial cells and antibodies to CD11b, LFA-1, VLA-4 and PSGL-1 for leukocytes. The data were expressed as mean ± SD. Statistical significance was determined by using unpaired Student T-test.
An increased number of leukocyte was observed trapped in retinal capillaries of diabetic mice compared to normal mice. Phenotype study indicated that majority of the entrapped cells were CD11b+ monocytes. Flow cytometry analysis of CD11b+ cells isolated from retinal tissue indicated an increased expression of ICAM-1 and VCAM-1 from diabetic mice compared to that of normal control mice. In addition, confocal microscopy of immunostained flatmount retina revealed only a tendency to an enhanced expression of VCAM-1 but not ICAM-1 in diabetic retinal vessels compared that in normal retinal vessels.
Our results indicate that CD11b+ monocytes may play an important role in capillary occlusion and thus contribute to diabetic retinopathy. The increased expression of VCAM-1 on retinal vascular endothelial cells might be responsible for monocyte entrapment in diabetes. Adhesion molecule ICAM-1 is up-regulated in retinal CD11b+ cells but possibly not in vascular endothelial cells in diabetes.
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