Pfister, F., 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Feng, Y., 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Hagen, F.V., 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Hoffmann, S., Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Molema, G., Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Hillebrands, J.-L., Department of Cell Biology, Section Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Shani, M., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Deutsch, U., Theodor Kocher Institute of Berne, Berne, Switzerland
Hammes, H.-P., 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Feng, Y., 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Hagen, F.V., 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Hoffmann, S., Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Molema, G., Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Hillebrands, J.-L., Department of Cell Biology, Section Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Shani, M., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Deutsch, U., Theodor Kocher Institute of Berne, Berne, Switzerland
Hammes, H.-P., 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
OBJECTIVE-The mechanism underlying pericyte loss during incipient diabetic retinopathy remains controversial. Hyperglycemia induces angiopoietin-2 (Ang-2) transcription, which modulates capillary pericyte coverage. In this study, we assessed loss of pericyte subgroups and the contribution of Ang-2 to pericyte migration. RESEARCH DESIGN AND METHODS-Numbers of total pericytes and their subgroups were quantified in retinal digest preparations of spontaneous diabetic XLacZ mice. Pericytes were divided into subgroups according to their localization, their position relative to adjacent endothelial cells, and the expression of LacZ. The contribution of Ang-2 to pericyte migration was assessed in Ang-2 overexpressing (mOpsinhAng2) and deficient (Ang2LacZ) mice. RESULTS-Pericyte numbers were reduced by 16% (P < 0.01) in XLacZ mice after 6 months of diabetes. Reduction of pericytes was restricted to pericytes on straight capillaries (relative reduction 27%, P < 0.05) and was predominantly observed in LacZ- positive pericytes (-20%, P < 0.01). Hyperglycemia increased the numbers of migrating pericytes (69%; P < 0.05), of which the relative increase due to diabetes was exclusively in LacZ-negative pericytes, indicating reduced adherence to the capillaries (176%; P < 0.01). Overexpression of Ang-2 in nondiabetic retinas mimicked diabetic pericyte migration of wild-type animals (78%; P < 0.01). Ang-2 deficient mice completely lacked hyperglycemia-induced increase in pericyte migration compared with wild- type littermates. CONCLUSIONS-Diabetic pericyte loss is the result of pericyte migration, and this process is modulated by the Ang-Tie system. © 2008 by the American Diabetes Association.
