He Jingliang, Yamane Mio, Shibata Shinsuke, Fukui Masaki, Shimizu Eisuke, Yano Tetsuya, Mukai Shin, Kawakami Yutaka, Li Shaowei, Tsubota Kazuo, Ogawa Yoko
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
Aier School of Ophthalmology, Central South University, Changsha, China.
Cornea. 2018 Apr;37(4):486-494. doi: 10.1097/ICO.0000000000001487.
To report the characteristics of the ocular surface in a previously established sclerodermatous chronic graft-versus-host disease (cGVHD) mouse model.
The ocular surface features and tear film parameters of the mouse model were assessed by histopathology, immunohistochemistry, electron microscopy, quantitative polymerase chain reaction, and flow cytometry.
The mice exhibited loss of body weight and decreased tear secretion (P < 0.001), mimicking the clinical features of patients with cGVHD. Ocular examination demonstrated significant corneal epithelial staining, conjunctival (P < 0.001), and eyelid (P = 0.015) fibrosis compared with the control mice. The density of both goblet cells (P = 0.043) and microvilli was lower (P < 0.001), and the microvilli were shorter (P = 0.007) in the conjunctiva of cGVHD mice than those of the controls. The immunohistochemical studies demonstrated greater expression of CD45, CD4, and CD8 cells in the conjunctiva and eyelid tissues compared with the controls (P < 0.05 for all). In addition, reduced Forkhead box P3 (Foxp3)+ cells were found in both the peripheral blood (P < 0.001) and conjunctiva (P = 0.042) of cGVHD mice compared with the controls.
The constellation of these findings suggests that the sclerodermatous cGVHD mouse model well recapitulates ocular manifestations of cGVHD in humans. This model can be used to study the mechanisms involved in the pathogenesis and treatment of chronic ocular graft-versus-host disease.
报告先前建立的硬皮病样慢性移植物抗宿主病（cGVHD）小鼠模型的眼表特征。
通过组织病理学、免疫组织化学、电子显微镜、定量聚合酶链反应和流式细胞术评估小鼠模型的眼表特征和泪膜参数。
小鼠体重减轻，泪液分泌减少（P < 0.001），模拟了cGVHD患者的临床特征。眼部检查显示，与对照小鼠相比，角膜上皮染色、结膜（P < 0.001）和眼睑（P = 0.015）纤维化明显。cGVHD小鼠结膜中的杯状细胞密度（P = 0.043）和微绒毛密度均较低（P < 0.001），且微绒毛较短（P = 0.007）。免疫组织化学研究表明，与对照相比，结膜和眼睑组织中CD45、CD4和CD8细胞的表达更高（所有P < 0.05）。此外，与对照相比，cGVHD小鼠外周血（P < 0.001）和结膜（P = 0.042）中的叉头框P3（Foxp3）+细胞减少。
这些发现表明，硬皮病样cGVHD小鼠模型很好地概括了人类cGVHD的眼部表现。该模型可用于研究慢性眼部移植物抗宿主病发病机制和治疗中涉及的机制。
