Essential Role of Leptin in Ischemia-Induced Retinal Neovascularization

Abstract

Abstract: : Purpose: Retinal neovascularization is the final common pathway to blindness in diabetic retinopathy, retinopathy of prematurity (ROP), and age-related macular degeneration. 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, but the pathophysiological role of leptin in retinal neovascularization is still unclear. In the present study, we investigated if leptin is involved in the progression of ischemia-induced retinal neovascularization. Methods: A mouse model of ROP was induced in leptin-deficient ob/ob (n = 9) and wild-type mice (n = 8) as previously described (IOVS 35:101-11, 1994). Retinal fluorescein angiography was performed by intracardiac perfusion of the mice with fluorescein-dextran in phosphate-buffered saline. Retinal neovascularization was evaluated by counting neovascular nuclei per eye cross-section in the vitreous. Localization of leptin receptor (Ob-R) was examined by immunohistochemistry. Results: After the induction of ROP, retinal angiography of wild-type mice showed extensive neovascularization, whereas the extent of neovascularization was markedly inhibited in ob/ob mice. Neovascular nuclei per eye cross-section in ob/ob mice (74.2 ± 4.4) was significantly reduced as compared with those in wild-type mice (98.9 ± 4.4, P < 0.01). Immunostaining of Ob-R protein was localized to retinal vasculature. Conclusion: The present study indicates that leptin plays a critical role in the progression of ischemia-induced retinal neovascularization. The agents inhibiting leptin action might be therapeutically useful to treat retinal neovascular diseases.

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