Retinal overexpression of angiopoietin-2 mimics diabetic retinopathy and enhances vascular damages in hyperglycemia.
Our previous data suggested that angiopoietin-2 (Ang-2) is linked to pericyte loss, thereby playing an important role in diabetic retinopathy. In this study, we investigated the effect of retinal overexpression of human Ang-2 (mOpsinhAng2 mouse) on vascular morphology in non-diabetic and streptozotozin-induced diabetic animals. Pericyte (PC) coverage and acellular capillary (AC) formation were quantitated in retinal digest preparations after 3 and 6 months of diabetes duration. The degree of retinopathy in non-diabetic mOpsinhAng2 mice at 3 months (-21% PC, +49% AC) was comparable to age-matched diabetic wild type mice. Diabetic mOpsinhAng2 mice exhibited significantly worse vascular pathology than wild type counterparts at 6 months. Quantitative PCR revealed that human Ang-2 mRNA was highly overexpressed in retinas of transgenic mice. Our data demonstrate that overexpression of Ang-2 in the retina enhances vascular pathology, indicating that Ang-2 plays an essential role in diabetic vasoregression via destabilization of pericytes.
Pfister
Frederick
F
5th Medical Clinic, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Wang
Yumei
Y
Schreiter
Kay
K
vom Hagen
Franziska
F
Altvater
Karin
K
Hoffmann
Sigrid
S
Deutsch
Urban
U
Hammes
Hans-Peter
HP
Feng
Yuxi
Y
D042702:Angiopoietin-2 / Q000235:genetics*; D000818:Animals; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D017931:DNA Primers; D003930:Diabetic Retinopathy / Q000473:pathology / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D051379:Mice; D008954:Models, Biological; D020286:Pericytes / Q000473:pathology / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000502:physiology* / Q000503:physiopathology; D012171:Retinal Vessels / Q000473:pathology / Q000503:physiopathology
D042702:Angiopoietin-2; D017931:DNA Primers; D012333:RNA, Messenger