Department of Ophthalmology, The First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Acta Ophthalmol. 2012 Nov;90(7):e512-23. doi: 10.1111/j.1755-3768.2012.02476.x. Epub 2012 Sep 20.
To evaluate the effect of ZY1, a novel 21-amino acid peptide from human placenta growth factor-1 (PlGF-1), against ocular neovascularization, and to study its possible toxicity to the retina and the underlying mechanism of antiangiogenic effect.
MTS assays, a modified Boyden chamber and Matrigel(™) were used to evaluate the effect of ZY1 on the proliferation, migration and tube formation of RF/6A rhesus macaque choroid-retina endothelial cells induced by vascular endothelial growth factor (VEGF) in vitro. The antiangiogenic effect of ZY1 was also studied with corneal micropocket angiogenesis assays and oxygen-induced retinopathy (OIR) assays in mice. Electrophysiological tests and histological examinations were used to study the possible toxicity of ZY1 against mouse neuroretina. Competitive ELISA and Western blotting were performed to elucidate the underlying mechanism of ZY1.
ZY1 inhibited VEGF-induced RF/6A proliferation, migration and tube formation. It also inhibited ocular neovascularization when applied to the corneal micropocket angiogenesis assays and OIR assays in mice. Electrophysiological tests and histological examinations revealed no evident functional or morphologic abnormalities in mouse neuroretina after ZY1 injection. ZY1 competed for binding to VEGFR-1 against PlGF and VEGF and inhibited VEGFR-1/ERK/AKT activation.
It is concluded that the novel peptide ZY1 is an effective inhibitor of ocular pathologic angiogenesis and may provide a promising alternative for ocular antiangiogenic therapy.
评估新型 21 肽 ZY1（来源于人胎盘生长因子-1）对眼部新生血管的作用，并研究其对视网膜的潜在毒性及其抗血管生成作用的机制。
采用 MTS 检测法、改良 Boyden 室法和 Matrigel（TM）基质胶法，体外评估 ZY1 对血管内皮生长因子（VEGF）诱导的食蟹猴脉络膜视网膜内皮细胞（RF/6A）增殖、迁移和管状结构形成的影响。通过角膜微囊血管生成实验和小鼠氧诱导视网膜病变（OIR）模型评估 ZY1 的抗血管生成作用。通过电生理测试和组织学检查，研究 ZY1 对小鼠神经视网膜的潜在毒性。采用竞争性 ELISA 和 Western blot 法，阐明 ZY1 的作用机制。
ZY1 抑制 VEGF 诱导的 RF/6A 增殖、迁移和管状结构形成。在角膜微囊血管生成实验和小鼠 OIR 模型中，ZY1 也抑制眼部新生血管形成。电生理测试和组织学检查显示，注射 ZY1 后小鼠神经视网膜未见明显功能或形态异常。ZY1 与 VEGFR-1 竞争结合 PlGF 和 VEGF，并抑制 VEGFR-1/ERK/AKT 激活。
新型肽 ZY1 是一种有效的眼部病理性血管生成抑制剂，可为眼部抗血管生成治疗提供一种有前途的选择。
