TY - JOUR
T1 - Angiopoietin-2 Causes Pericyte Dropout in the Normal Retina
T2 - Evidence for Involvement in Diabetic Retinopathy
AU - Hammes, Hans Peter
AU - Lin, Jihong
AU - Wagner, Patrick
AU - Feng, Yuxi
AU - Vom Hagen, Franziska
AU - Krzizok, Thomas
AU - Renner, Oliver
AU - Breier, Georg
AU - Brownlee, Michael
AU - Deutsch, Urban
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=12144286666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12144286666&partnerID=8YFLogxK
U2 - 10.2337/diabetes.53.4.1104
DO - 10.2337/diabetes.53.4.1104
M3 - Article
C2 - 15047628
AN - SCOPUS:12144286666
SN - 0012-1797
VL - 53
SP - 1104
EP - 1110
JO - Diabetes
JF - Diabetes
IS - 4
ER -