Inhibitory role of adiponectin peptide I on rat choroidal neovascularization.

Inhibitory role of adiponectin peptide I on rat choroidal neovascularization.
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DOI:
10.1016/j.bbamcr.2012.05.017
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发表时间:
2012-08
影响因子:
5.1
通讯作者:
Bora, Puran S.
Bora, Puran S.
中科院分区:
生物学2区
文献类型:
--
作者:
Lyzogubov, Valeriy V.;Tytarenko, Ruslana G.;Bora, Nalini S.;Bora, Puran S.

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年龄相关性黄斑变性(AMD)是老年人中枢性失明的主要原因。湿型AMD的特点是新血管的广泛生长。限制脉络膜新生血管(CNV)是治疗湿性AMD的有效策略之一。我们研究了脂联素肽I (APNpI)对激光诱导大鼠湿性AMD模型新生血管生长和脉络膜内皮细胞(CEC)培养的影响。显微镜下观察CNV大小和血管密度。对CNV区血管性血友病因子(vWF)、APN、APN受体1 (AdipoR1)、2 (AdipoR2)、VEGF、VEGF受体2 (VEGF- r2)、增殖细胞核抗原(PCNA)进行免疫组化染色。采用RT-PCR和real-time PCR检测rpe -脉络膜中VEGF和VEGF- r2 mRNA的表达。APNpI抑制CNV面积4倍,抑制vWF阳性血管数99%,抑制视网膜下组织面积40%。APNpI处理后,VEGF和VEGF- r2在mRNA和蛋白水平上的表达均降低。APNpI治疗大鼠激光斑的增殖指数(PCNA)比对照组低5倍。综上所述,APNpI通过降低VEGF、VEGF- r2表达和细胞增殖抑制CNV模型大鼠新生血管的形成。因此,APNpI可能具有潜在的治疗用途,因为它可以显著抑制CNV。
Age-related macular degeneration (AMD) is a leading cause of central blindness in elderly population. Wet type of AMD is characterized by extensive growth of new vessels. One of the effective strategies to treat wet AMD is to limit the choroidal neovascularization (CNV). We studied effect of adiponectin peptide I (APNpI) on new vessel growth in laser-induced rat model of wet AMD and on rat choroidal endothelial cell (CEC) culture. CNV size and vessel density was investigated by microscopy. Immunohistochemical staining (IHC) for Von Willebrand Factor (vWF), APN, APN receptors 1 (AdipoR1), 2 (AdipoR2), VEGF, VEGF receptor 2 (VEGF-R2), proliferating cell nuclear antigen (PCNA) was performed in CNV area. The mRNA expression of VEGF and VEGF-R2 in RPE-choroid was investigated by RT-PCR and real-time PCR. APNpI inhibited area of CNV by 4 fold, number of vWF positive vessels by 99% and area of subretinal tissue by 40%. The expression of VEGF and VEGF-R2 at mRNA and protein levels were decreased after APNpI treatment in vivo. Proliferative index (PCNA) was 5 fold less in laser spots of APNpI treated rats compared to controls. In conclusion, APNpI inhibited formation of new vessels in rat model of CNV by decreasing VEGF, VEGF-R2 expression and cell proliferation. Thus, APNpI may have potential therapeutic use for AMD treatment since it significantly inhibited CNV.
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