Pericyte migration: A novel mechanism of pericyte loss in experimental diabetic retinopathy
- Frederick Pfister1,
- Dr. Yuxi Feng1,
- Franziska vom Hagen1,3,
- Dr. Sigrid Hoffmann2,
- Prof. Grietje Molema3,
- Jan-Luuk Hillebrands, PhD4,
- Moshe Shani, PhD5,
- Dr. Urban Deutsch6 and
- Prof. Hans-Peter Hammes (hans-peter.hammes{at}med5.ma.uni-heidelberg.de)1
- 15th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- 2Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
- 3Dept. of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Netherlands
- 4Dept. Cell Biology, Section Immunology, University Medical Center Groningen, University of Groningen, Netherlands
- 5Institute of Animal Science, The Volcani Center, Bet Dagan, Israel
- 6Theodor Kocher Institute of Berne, Berne, Switzerland
Abstract
Objective: The mechanism underlying pericyte (PC) loss during incipient diabetic retinopathy remains controversial. Hyperglycemia induces angiopoietin-2 (Ang-2) transcription, which modulates capillary PC coverage. In this study, we assessed loss of PC subgroups and the contribution of Ang-2 to PC migration.
Research Design and Methods: Numbers of total PCs and their subgroups were quantified in retinal digest preparations of spontaneous diabetic XLacZ mice. PCs 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 PC 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 predominantly observed in LacZ positive PCs (-20 %, p < 0.01). Hyperglycemia increased the numbers of migrating PCs (+69%; p < 0.05), of which the relative increase due to diabetes was exclusively in LacZ negative PCs, indicating reduced adherence to the capillaries (+176%; p < 0.01). Overexpression of Ang-2 in nondiabetic retinas mimicked diabetic PC migration of wild-type animals (+78%; p < 0.01). Ang-2 deficient mice completely lacked hyperglycemia-induced increase in pericyte migration compared to wild-type littermates.
Conclusion: Diabetic pericyte loss is the result of pericyte migration and this process is modulated by the Ang-Tie system.
Footnotes
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- Received March 6, 2008.
- Accepted June 7, 2008.
- Copyright © American Diabetes Association
