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Yasuhiro Iesato, Takayuki Sakurai, Akiko Kamiyoshi, Yuka Shido, Teruhide Koyama, Akihiro Yamauchi, Takayuki Shindo, Toshinori Murata; Angiogenic Potency Of Endogenous Adrenomedullin In Mouse Model Of Oxygen-induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3166.
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Adrenomedullin (AM), originally identified as a vasodilating peptide, has been shown to exist in the whole body and exert various biological functions, including anti-oxidative effect, anti-inflammatory effect, anti-thrombotic effect, and to regulate several hormonal secretions. We have established genetically engineered mice that show altered expression of AM and its related molecules. We demonstrated that homozygotes of AM knockout mice (AM-/-) were embryonic lethal with abnormalities of vascular development and clarified that AM is also an angiogenic factor. AM is also expressed in the eye including retina, however ocular functions of AM are little known. In the current study, we analyzed angiogenic potency of endogenous AM in retina by oxygen-induced retinopathy (OIR) model using AM knockout mice.
Wild-type C57BL/6 mice (WT) and heterozygotic AM knockout mice (AM+/-) were exposed to 75% oxygen from postnatal day (P)7 to P12 and returned to room air. Both genotypes of mice, which were kept in room air, were used for control. Eyes were collected at P17 and mRNA was extracted from retinas to analyze the gene expression including AM and its related molecules by quantitative real-time PCR. Retinal neovascularization, avascular area, and hypoxic area were analyzed using flat-mount specimens of retina stained with isolectin B4 and hypoxyprobe-1. Neovascularization was also assessed in retinal sections by hematoxylin-eosin staining.
Both in WT and AM+/- retinas with OIR, AM expression was upregulated than those in room air. In the OIR, neovascularization, avascular area and hypoxic area in AM+/- was significantly reduced than that in WT.
We first found that endogenous AM is crucially involved in retinal angiogenesis. Modulation of AM-signaling could be applied for the management of retinal neovascularization in future.
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