Purchase this article with an account.
Y. Ito, Y. Takihara, M. Fukushima, M. Inatani, Y. Oike, H. Tanihara; Angptl2 Induces Inflammation of Retinal Vessels in Diabetes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5607.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Angiopoietin-like protein 2 (Angptl2), we identified recently, is closely related to adiposity, systemic insulin resistance and inflammation in diabetes, and also promotes angiogenesis and vascular leakiness in vivo. Moreover, we found that serum Angptl2 was significantly increased in patients with type 2 diabetes. However, the role of Angptl2 in diabetic retinopathy is still unknown. In this study, we investigated the role of Angptl2 in diabetic retinopathy.
Pars plana vitrectomy (PPV) was performed on proliferative diabetic retinopathy (n=20) and macular hole or epiretinal membrane (control group; n=20). At the beginning of PPV, undiluted core vitreous samples were collected, and immediately transferred on ice. The specimens were stored at -80°C until the measurement. The concentration of Angptl2 in vitreous samples was measured using sandwich enzyme-linked immunosorbent assay (ELISA). Furthermore, we obtained the proliferative membrane in PDR during PPV, and performed immunohistochemical analysis for Angptl2. Informed consent was obtained from all patients prior to the interventions. This study was approved by the Clinical Research Ethics Committee of Kumamoto University. Next we induced diabetes in C57BL/6 and Angptl2-deficient mice by streptozotocin. Leukocyte adhesion to the retinal vessels was evaluated with a concanavalin A lectin staining. Intercellular adhesion molecule-1 (ICAM-1) expression level in diabetic mouse retina was examined by ELISA. Finally, we examined whether Angptl2 upregulated ICAM-1 expression and phosphorylated NFΚB in human retinal endothelial cells (HRECs) in vitro.
The vitreous concentration of Angptl2 in PDR (4.77 ± 0.89ng/ml) was statistically significant compared with the control eyes (1.03 ± 0.11ng/ml) (P<0.001), and Angptl2 was highly expressed in the proliferative membrane in PDR. Leukocyte adhesion to the retinal vessels was suppressed in diabetic Angptl2-deficient mice compared with C57BL/6. ICAM-1 expression in diabetic retina was also suppressed in Angptl2-deficient mice. In addition, we found that Angptl2 upregulated ICAM-1 expression and phosphorylated NFΚB in HRECs.
The pathogenesis of diabetic retinopathy is mediated by inflammation. Our data provide Angptl2 may develop inflammation on retinal vessels via NFΚB signaling in diabetic patients. These novel findings indicate Angptl2 as a therapeutic target for the treatment of diabetic retinopathy.
This PDF is available to Subscribers Only