Abstract
Purpose: :
Fatty acid binding protein 4 (FABP4) is a member of the FABP family, which consists of small molecular weight, highly conserved proteins that function as chaperones for free fatty acids. FABP4 plays a critical role in maintenance of glucose and lipid homeostasis as well as in the regulation of inflammation. Initially, FABP4 was thought to be expressed primarily by adipocytes and macrophages. We recently determined that FABP4 is also expressed in certain endothelial cells (ECs) in normal tissues where it plays a pro-angiogenic role. We also showed that FABP4 expression in ECs is up-regulated by the VEGF/VEGFR2 pathway. The goal of this study was to determine whether FABP4 plays a role in oxygen-induced retinal neovascularization.
Methods: :
Oxygen-induced retinopathy (OIR) was induced by exposing wild type (wt) and FABP4 -/- mouse pups to 75% oxygen between postnatal (P) days 7 and 12. At P12, P15 and P17, retinas were harvested for mRNA analysis by quantitative PCR (qPCR). Retinal whole-mounts were immunolabeled for EC using isolectin-B4 and for FABP4. Avascular and neovascular areas were quantified at P12 and P17 using Photoshop CS4 software.
Results: :
FABP4 mRNA levels were significantly increased in the OIR wt mice compared to the control mice at P15 (p < 0.01). Immunostaining revealed that FABP4 was strongly expressed in the endothelium of the new vessels but absent in normal retinal vessels. At P12, the area of the hyperoxia-induced vaso-obliteration was slightly increased in FABP4-/-. However, both the neovascular and avascular areas of FABP4-/- retinas were significantly reduced at P17 compared to WT (by 40% and 20%, respectively).
Conclusions: :
FABP4-deficient mice are significantly protected from OIR. Restricted expression of FABP4 to neovascular tufts in the OIR model suggests that inhibition FABP4 may have minimal side effects on non-pathological retinal vessels and suggests it may have potential as a therapeutic target.
Keywords: retinopathy of prematurity • retinal neovascularization • retina