Leptin stimulates ischemia-induced retinal neovascularization: Possible role of vascular endothelial growth factor expressed in retinal endothelial cells

Eri Suganami, Hitoshi Takagi, Hirokazu Ohashi, Kiyoshi Suzuma, Izumi Suzuma, Hideyasu Oh, Daisuke Watanabe, Tomonari Ojima, Takayoshi Suganami, Yasushi Fujio, Kazuwa Nakao, Yoshihiro Ogawa, Nagahisa Yoshimura

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

Abstract

Diabetic retinopathy is the leading cause of new blindness in adults in developed countries. Leptin, an adipocyte-derived hormone, stimulates endothelial proliferation and angiogenesis. This study was designed to elucidate the pathophysiologic role of leptin in the progression of retinal neovascularization. Using the retinopathy of prematurity model, a mouse model of ischemia-induced retinal neovascularization, we have demonstrated more pronounced retinal neovascularization in 17-day-old transgenic mice overexpressing leptin than in age-matched wild-type littermates. Ischemia-induced retinal neovascularization was markedly suppressed in 17-day-old leptin-deficient ob/ob mice. Western blot analysis revealed that a biologically active leptin receptor isoform is expressed in mouse retinal endothelial cells. Leptin receptor expression was also detected in primary cultures of porcine retinal endothelial cells, where it upregulated vascular endothelial growth factor (VEGF) mRNA expression. This effect was thought to be mediated at least partly through the activation of signal transducers and activators of transcription (STAT)3, because adenoviral transfection of the dominant-negative form of STAT3 abolished the leptin-induced upregulation of VEGF mRNA expression in retinal endothelial cells. This study provides evidence that leptin stimulates the ischemia-induced retinal neovasucularization possibly through the upregulation of endothelial VEGF, thereby suggesting that leptin antagonism may offer a novel therapeutic strategy to prevent or treat diabetic retinopathy.

Original languageEnglish
Pages (from-to)2443-2448
Number of pages6
JournalDiabetes
Volume53
Issue number9
DOIs
Publication statusPublished - Sep 1 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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