Periostin in vitreoretinal diseases
Periostin in vitreoretinal diseases
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DOI：
10.1007/s00018-017-2651-5
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发表时间：
2017-09
影响因子：
8
通讯作者：
S. Yoshida;Takahito Nakama;K. Ishikawa;S. Nakao;K. Sonoda;T. Ishibashi
中科院分区：
文献类型：
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作者：
S. Yoshida;Takahito Nakama;K. Ishikawa;S. Nakao;K. Sonoda;T. Ishibashi
在发达国家，诸如糖尿病性视网膜病变、增殖性玻璃体视网膜病变（PVR）和年龄相关性黄斑变性的增殖性玻璃体视网膜疾病是视力下降和失明的主要原因。在这些疾病中，视网膜上方和下方的视网膜血管膜（FVM）形成起着重要作用。人FVM的基因表达谱显示骨膜蛋白的显著上调。随后的分析表明，增殖性糖尿病视网膜病变和PVR患者玻璃体中的骨膜蛋白表达增加。免疫组织化学分析显示骨膜蛋白与α-SMA和M2巨噬细胞标志物在FVM中共定位。在体外实验中，骨膜蛋白阻断剂可抑制PVR玻璃体和转化生长因子-β2（TGF-β2）诱导的移行和粘附。在体内，靶向骨膜蛋白的新型单链RNAi剂显示出对实验性视网膜和脉络膜FVM形成的抑制作用，而不影响视网膜细胞的活力。这些结果表明，骨膜蛋白是FVM形成的关键分子，是这些增殖性玻璃体视网膜疾病的有希望的治疗靶点。
Proliferative vitreoretinal diseases such as diabetic retinopathy, proliferative vitreoretinopathy (PVR), and age-related macular degeneration are a leading cause of decreased vision and blindness in developed countries. In these diseases, retinal fibro(vascular) membrane (FVM) formation above and beneath the retina plays an important role. Gene expression profiling of human FVMs revealed significant upregulation of periostin. Subsequent analyses demonstrated increased periostin expression in the vitreous of patients with both proliferative diabetic retinopathy and PVR. Immunohistochemical analysis showed co-localization of periostin with α-SMA and M2 macrophage markers in FVMs. In vitro, periostin blockade inhibited migration and adhesion induced by PVR vitreous and transforming growth factor-β2 (TGF-β2). In vivo, a novel single-stranded RNAi agent targeting periostin showed the inhibitory effect on experimental retinal and choroidal FVM formation without affecting the viability of retinal cells. These results indicated that periostin is a pivotal molecule for FVM formation and a promising therapeutic target for these proliferative vitreoretinal diseases.