| First Author | Higuchi A | Year | 2010 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 30 |
| Issue | 1 | Pages | 46-53 |
| PubMed ID | 19910632 | Mgi Jnum | J:171798 |
| Mgi Id | MGI:4999714 | Doi | 10.1161/ATVBAHA.109.198465 |
| Citation | Higuchi A, et al. (2010) Thiazolidinediones reduce pathological neovascularization in ischemic retina via an adiponectin-dependent mechanism. Arterioscler Thromb Vasc Biol 30(1):46-53 |
| abstractText | 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. |
