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Arterioscler Thromb Vasc Biol. 2010 Jan;30(1):46-53. doi: 10.1161/ATVBAHA.109.198465. Epub 2009 Nov 12.

Thiazolidinediones reduce pathological neovascularization in ischemic retina via an adiponectin-dependent mechanism.

Author information

1
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany St, W611, Boston, MA 02118, USA.

Abstract

Background- The insulin-sensitizing agents referred to as thiazolidinediones (TZDs) possess antiatherogenic and anti-inflammatory actions that contribute to protection against diabetic macrovascular complications. However, little is known about the effects of TZDs on retinal microvessel disorders.

OBJECTIVE:

To investigate whether TZDs modulate retinal vessel formation in a mouse model of oxygen-induced retinopathy.

METHODS AND RESULTS:

Neonatal mice were subjected to ischemia-induced retinopathy to produce pathological neovascular tuft formation. Pioglitazone, 10 mg/kg per day, rosiglitazone, 10 mg/kg per day, or vehicle was given by gavage once a day from postnatal day 7 to postnatal day 17. Systemic treatment of wild-type (WT) mice with TZDs led to a significant decrease in pathological retinal neovascularization during ischemia compared with vehicle treatment, which was accompanied by increased plasma levels of the fat-derived hormone adiponectin (APN). In contrast to WT mice, TZDs had no effects on ischemia-induced pathological retinal vessel formation in APN-knockout (KO) mice. Pioglitazone reduced tumor necrosis factor (TNF) alpha expression in ischemic retina in WT mice but not in APN-KO mice. Furthermore, pioglitazone increased plasma APN levels in TNF-alpha-KO mice but did not affect ischemia-induced pathological retinal neovascularization in this strain.

CONCLUSIONS:

These data show that TZDs attenuate pathological retinal microvessel formation through APN-mediated modulation of TNF-alpha production.

PMID:
19910632
PMCID:
PMC3552615
DOI:
10.1161/ATVBAHA.109.198465
[Indexed for MEDLINE]
Free PMC Article

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