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E. Suganami, H. Takagi, K. Suzuma, I. Suzuma, Y. Ogawa, K. Nakao, N. Yoshimura, Y. Honda; Leptin Promotes Retinal Neovascularization through VEGF Upregulation in Endothelial Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2886.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The adipocyte-derived cytokine leptin is a circulating hormone and regulates energy metabolism and food intake. Recently, it has been shown that leptin possesses an angiogenic properties and that the plasma as well as vitreous leptin level is increased in patients with diabetic retinopathy. We have already reported that ischemia-induced retinal neovascularization was significantly inhibited in leptin-deficient ob/ob mice. In the present study, we investigated the molecular mechanisms how leptin is involved in retinal neovascularization.Methods: Retinopathy of prematurity (ROP) was induced in mice as previously described (IOVS 35:101-11, 1994). Localization of leptin receptor (Ob-R) was examined by immunohistochemistry. In cultured porcine retinal endothelial cells (PREC), the effects of leptin on vascular endothelial growth factor (VEGF) expression and the intracellular signaling pathway were examined by Northern blotting and Western blotting.Results: Expression of Ob-R was localized to the retinal vasculature, predominantly in endothelial cells. Immunostaining of Ob-R was markedly intensed in ROP mice as compared with that in control mice. In cultured PREC, treatment of leptin not only showed significant upregulation of VEGF expression (up to +57% of basal), but also intensified hypoxia-induced VEGF expression. Leptin also induced phosphorylation of STAT3 and ERK/MAP kinase in cultured PREC (up to +153% and +92%, respectively).Conclusions: The present study suggests that leptin plays a role in the progression of ischemia-induced retinal neovascularization by induction of VEGF. The prevention of leptin-associated mechanisms in retinal neovascularization might be therapeutically useful to treat retinal neovascular diseases.
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