Angiopoietin-2 deficiency decelerates age-dependent vascular changes in the mouse retina

Feng, Yuxi; Pfister, Frederick; Schreiter, Kay; Wang, Yumei; Stock, Oliver; Vom Hagen, Franziska; Wolburg, Hartwig; Hoffmann, Sigrid; Deutsch, Urban; Hammes, Hans-Peter (2008). Angiopoietin-2 deficiency decelerates age-dependent vascular changes in the mouse retina. Cellular physiology and biochemistry, 21(1-3), pp. 129-36. Basel: Karger 10.1159/000113755

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Retinae of aged humans show signs of vascular regression. Vascular regression involves a mismatch between Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) expression. We used heterozygous Ang-2 deficient (Ang2LacZ) mice to evaluate murine retinal vascular changes and gene expression of growth factors. Vascular changes were assessed by quantitative retinal morphometry and gene expression levels of growth factors were measured by quantitative PCR. The numbers of endothelial cells and pericytes did not change in the Ang2LacZ retinae with age, whereas they decreased throughout the age spectrum studied in the wild type retinae. Moreover, vascular regression significantly decelerated in the heterozygous Ang2LacZ retinae (200% to 1 month), while the formation of acellular capillaries was significantly increased at 13 months in the wild type retinae (340% to 1 month). Gene expression analysis revealed that VEGF, Ang-1, PDGF-B and Ang2 mRNA levels were decreased in the wild type retinae at 9 month of age. However, the decrease of Ang-2 was smaller compared with other genes. While VEGF levels dropped in wild type mice up to 60% compared to 1 month, VEGF increased in heterozygous Ang-2 deficient retinae at an age of 9 months (141% to 1 month). Similarly, Ang-1 levels decreased in wild type mice (45% to 1 month), but remained stable in Ang2LacZ mice. These data suggest that Ang-2 gene dose reduction decelerates vasoregression in the retina with age. This effect links to higher levels of survival factors such as VEGF and Ang-1, suggesting that the ratio of these factors is critical for capillary cell survival.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Deutsch, Urban

ISSN:

1015-8987

ISBN:

18209480

Publisher:

Karger

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:55

Last Modified:

04 May 2014 23:16

Publisher DOI:

10.1159/000113755

PubMed ID:

18209480

Web of Science ID:

000252589900014

URI:

https://boris.unibe.ch/id/eprint/23660 (FactScience: 43324)

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