title: Angiopoietin-2 causes pericyte dropout in the normal retina: evidence for involvement in diabetic retinopathy.
abstract: 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.
authors.affiliation: 5th Medical Clinic, University-Clinic Mannheim, Medical Faculty of the University of Heidelberg, Heidelberg, Germany. hans-peter.hammes@med5.uni-heidelberg.de
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.forename: Jihong
authors.initials: J
authors.lastname: Lin
authors.forename: Patrick
authors.initials: P
authors.lastname: Wagner
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Feng
authors.forename: Franziska
authors.initials: F
authors.lastname: Vom Hagen
authors.forename: Thomas
authors.initials: T
authors.lastname: Krzizok
authors.forename: Oliver
authors.initials: O
authors.lastname: Renner
authors.forename: Georg
authors.initials: G
authors.lastname: Breier
authors.forename: Michael
authors.initials: M
authors.lastname: Brownlee
authors.forename: Urban
authors.initials: U
authors.lastname: Deutsch
mesh_terms: D042683:Angiopoietin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D042702:Angiopoietin-2 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002196:Capillaries / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000473:pathology*; D006442:Glycated Hemoglobin / Q000032:analysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020286:Pericytes / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D012171:Retinal Vessels / Q000166:cytology*; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D001616:beta-Galactosidase