Fukui Masaki, Ogawa Yoko, Mukai Shin, Kamoi Mizuka, Asato Teru, Kawakami Yutaka, Tsubota Kazuo
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
J Ophthalmol. 2017;2017:1639012. doi: 10.1155/2017/1639012. Epub 2017 Sep 30.
To investigate whether the SNARE protein vesicle-associated membrane protein 8 (VAMP8) was implicated in the development of chronic ocular graft-versus-host disease (GVHD).
Firstly, the chronic GVHD (cGVHD) and Sjögren's syndrome (SS)-impaired lacrimal gland (LG) tissue sections from humans for diagnostic purpose were evaluated for VAMP8 expression by histopathology and immunohistochemistry. Next, serial changes of tear secretion and VAMP8 expression at both protein and mRNA level of LG in an animal cGVHD model compared with the syngeneic control.
Decreased VAMP 8 expression in the cGVHD-affected human LG was detected in comparison with SS-affected LG. Tear secretion in the murine cGVHD model was significantly reduced compared with that in the syngeneic controls 8 weeks after BMT. Protein expression of VAMP8 in the cGVHD-affected LG in murine cGVHD was decreased in comparison with that in the controls. Gene expression of VAMP8 in the cGVHD-affected murine LG was significantly less than that in the syngeneic control 3 weeks after BMT.
Our results suggested that expression of VAMP8 in the cGVHD-affected LG was decreased and accordingly tear secretion in cGVHD was reduced. Collectively, the reduction of VAMP8 expression in the cGVHD-affected LG can be involved in the pathogenic processes of cGVHD-induced dry eye disease.
研究可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体(SNARE)蛋白囊泡相关膜蛋白8(VAMP8)是否与慢性眼部移植物抗宿主病(GVHD)的发生发展有关。
首先,通过组织病理学和免疫组织化学评估用于诊断目的的人类慢性GVHD(cGVHD)和干燥综合征(SS)受损泪腺(LG)组织切片中VAMP8的表达。其次,将动物cGVHD模型中LG的泪液分泌以及蛋白质和mRNA水平的VAMP8表达的系列变化与同基因对照进行比较。
与SS受累的LG相比,在受cGVHD影响的人类LG中检测到VAMP 8表达降低。与同基因对照相比,小鼠cGVHD模型在骨髓移植后8周时泪液分泌显著减少。与对照相比,小鼠cGVHD中受cGVHD影响的LG中VAMP8的蛋白质表达降低。骨髓移植后3周,受cGVHD影响的小鼠LG中VAMP8的基因表达明显低于同基因对照。
我们的结果表明,受cGVHD影响的LG中VAMP8的表达降低,因此cGVHD中的泪液分泌减少。总体而言,受cGVHD影响的LG中VAMP8表达的降低可能参与了cGVHD诱导的干眼病的发病过程。