Adiponectin suppresses pathological microvessel formation in retina through modulation of tumor necrosis factor-alpha expression.

Abstract:

:The fat-derived hormone adiponectin has been shown to have a protective role in macrovascular disorders. However, nothing is known about the function of adiponectin in retinal microvessel disease. Here, we investigated the causal role of adiponectin in retinal vessel formation and inflammation under conditions of hypoxia. When neonatal mice were subjected to ischemia-induced retinopathy, pathological retinal neovascularization during ischemia was exacerbated in adiponectin-knockout (APN-KO) mice compared with wild-type mice (neovascular area: 17.0+/-1.0% versus 11.7+/-0.6%, respectively). APN-KO mice also exhibited increased leukocyte adhesion (2.3+/-0.4-fold) and tumor necrosis factor (TNF)-alpha expression (2.6+/-0.2-fold) in hypoxic retina. Adenovirus-mediated overexpression of adiponectin attenuated hypoxia-induced pathological retinal neovascularization by 35% in wild-type mice and by 40% in APN-KO mice and leukostasis by 64% in wild-type mice and by 75% in APN-KO mice, which were associated with reduced TNF-alpha production. TNF-alpha blockade diminished the enhanced pathological neovascularization in APN-KO mice by 34%, and the inhibitory effects of adiponectin overexpression on retinal neovascularization and leukocyte adhesion were abolished in mice lacking TNF-alpha. These data provide evidence that adiponectin protects against retinal vessel injury following pathological stimuli through modulation of TNF-alpha inflammatory responses.

journal_name

Circ Res

journal_title

Circulation research

authors

Higuchi A,Ohashi K,Kihara S,Walsh K,Ouchi N

doi

10.1161/CIRCRESAHA.109.194506

subject

Has Abstract

pub_date

2009-05-08 00:00:00

pages

1058-65

issue

9

eissn

0009-7330

issn

1524-4571

pii

CIRCRESAHA.109.194506

journal_volume

104

pub_type

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