Retinal overexpression of angiopoietin-2 mimics diabetic retinopathy and enhances vascular damages in hyperglycemia

被引:85
作者
Pfister, Frederick [1 ]
Wang, Yumei [1 ]
Schreiter, Kay [2 ]
vom Hagen, Franziska [1 ]
Altvater, Karin [1 ]
Hoffmann, Sigrid [3 ]
Deutsch, Urban [4 ]
Hammes, Hans-Peter [1 ]
Feng, Yuxi [1 ]
机构
[1] Univ Heidelberg, Med Fac Mannheim, Med Clin 5, D-68167 Mannheim, Germany
[2] DeveloGen AG, D-37079 Gottingen, Germany
[3] Univ Heidelberg, Med Fac Mannheim, Med Res Ctr, D-68167 Mannheim, Germany
[4] Univ Bern, Theodor Kocher Inst, CH-3012 Bern, Switzerland
关键词
Angiopoietin-2; Diabetic retinopathy; Pericyte; GROWTH-FACTOR; MULLER CELLS; ANGIOGENESIS; EXPRESSION;
D O I
10.1007/s00592-009-0099-2
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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.
引用
收藏
页码:59 / 64
页数:6
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