Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hammes, H.-P.
Right arrow Articles by Deutsch, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hammes, H.-P.
Right arrow Articles by Deutsch, U.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 53:1104-1110, 2004
© 2004 by the American Diabetes Association, Inc.

Angiopoietin-2 Causes Pericyte Dropout in the Normal Retina

Evidence for Involvement in Diabetic Retinopathy

Hans-Peter Hammes1, Jihong Lin1, Patrick Wagner2, Yuxi Feng1, Franziska vom Hagen1, Thomas Krzizok3, Oliver Renner4, Georg Breier2, Michael Brownlee5, and Urban Deutsch2,6

1 5th Medical Clinic, University-Clinic Mannheim, Medical Faculty of the University of Heidelberg, Heidelberg, Germany
2 Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany
3 Department of Neuroophthalmology, Justus-Liebig-University, Giessen, Germany
4 Spanish National Cancer Centre (CNIO), Experimental Therapies Program, Madrid, Spain
5 Diabetes Research Center, Departments of Medicine and Pathology, Albert Einstein College of Medicine, Bronx, New York
6 Max Planck Institute for Vascular Biology, Department of Vascular Cell Biology, Muenster, Germany

Pericyte loss is an early pathologic feature of diabetic retinopathy, consistently present in retinae of diabetic humans and animals. Because pericyte recruitment and endothelial cell survival are controlled, in part, by the angiopoietin/Tie2 ligand/receptor system, we studied the expression of angiopoietin-2 and -1 in relation to the evolution of pericyte loss in diabetic rat retinae, using quantitative retinal morphometry, and in retinae from mice with heterozygous angiopoietin deficiency (Ang-2 LacZ knock-in mice). Finally, recombinant angiopoietin-2 was injected into eyes of nondiabetic rats, and pericyte numbers were quantitated in retinal capillaries. Angiopoietin-1 protein was present in the normal maturing retina and was upregulated 2.5-fold in diabetic retinae over 3 months of diabetes. In contrast, angiopoietin-2 protein was consistently upregulated more than 30-fold in the retinae of diabetic rats, preceding the onset of pericyte loss. Heterozygous angiopoietin-2 deficiency completely prevented diabetes-induced pericyte loss and reduced the number of acellular capillary segments. Injection of angiopoietin-2 into the eyes of normal rats induced a dose-dependent pericyte loss. These data show that upregulation of angiopoietin-2 plays a critical role in the loss of pericytes in the diabetic retina.

Address correspondence and reprint requests to Hans-Peter Hammes, MD, PhD, e-mail: hans-peter.hammes{at}med5.ma.uni-heidelberg.de, or Urban Deutsch, PhD, e-mail: u.deutsch{at}mpi-muenster.mpg.de


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.