Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan; Department of Ophthalmology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Aier School of Ophthalmology, Central South University, Changsha, China.
Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan; Department of Ophthalmology, Kyorin University, School of Medicine, Tokyo, Japan.
Ocul Surf. 2022 Oct;26:328-341. doi: 10.1016/j.jtos.2021.10.006. Epub 2021 Oct 26.
To investigate pathological changes in blood vessels and meibomian glands (MGs) in the eyelids of sclerodermatous chronic graft-versus-host disease (cGVHD) model mice.
We used an established major histocompatibility complex compatible, multiple minor histocompatibility antigen-mismatched sclerodermatous cGVHD mouse model. Blood vessels and MGs of eyelids from allogeneic bone marrow transplantation (allo-BMT) recipient mice and syngeneic bone marrow transplantation (syn-BMT) recipient mice were assessed by histopathology, immunohistochemistry and transmission electron microscopy. Peripheral blood samples from the recipients were examined by flow cytometry.
Allo-BMT samples showed dilating, tortuous and branching vessels and shrunk MGs in the eyelids; showed significantly higher expression of VEGFR2 (p = 0.029), CD133 (p = 0.016), GFP (p = 0.006), and α-SMA (p = 0.029) in the peripheral MG area; showed endothelial damage and activation, fibrotic change, and immune cell infiltration into MGs compared with syn-BMT samples. Fewer Ki-67 cells were observed in allo- and syn-BMT samples than in wild-type samples (p = 0.030). Ultrastructural changes including endothelial injury and activation, fibroblast activation, granulocyte degranulation, immune cell infiltration into MGs, and necrosis, apoptosis of MG basal cells were found in allo-BMT samples compared with syn-BMT samples.
A series of our studies indicated that cGVHD can cause eyelid vessel and MGs changes, including endothelial injury and activation, neovascularization, early fibrotic changes, immune cell infiltration, MG basal cell necrosis and apoptosis, and resultant MG atrophy.
研究硬皮病样慢性移植物抗宿主病（cGVHD）模型小鼠眼睑血管和睑板腺（MGs）的病理学变化。
我们使用了一种已建立的主要组织相容性复合物相容、多个次要组织相容性抗原不匹配的硬皮病样 cGVHD 小鼠模型。通过组织病理学、免疫组织化学和透射电子显微镜评估异基因骨髓移植（allo-BMT）受者和同基因骨髓移植（syn-BMT）受者小鼠眼睑的血管和 MGs。通过流式细胞术检查受者的外周血样本。
allo-BMT 样本显示眼睑扩张、扭曲和分支血管以及收缩的 MGs；在周围 MG 区域，VEGFR2（p=0.029）、CD133（p=0.016）、GFP（p=0.006）和α-SMA（p=0.029）的表达显著升高；与 syn-BMT 样本相比，显示内皮损伤和激活、纤维化改变以及免疫细胞浸润到 MGs 中。与野生型样本相比，allo-和 syn-BMT 样本中的 Ki-67 细胞较少（p=0.030）。与 syn-BMT 样本相比，allo-BMT 样本中发现内皮损伤和激活、成纤维细胞激活、粒细胞脱颗粒、免疫细胞浸润到 MGs 中以及 MG 基底细胞坏死和凋亡等超微结构变化。
我们的一系列研究表明，cGVHD 可引起眼睑血管和 MGs 变化，包括内皮损伤和激活、新生血管形成、早期纤维化改变、免疫细胞浸润、MG 基底细胞坏死和凋亡，以及由此导致的 MGs 萎缩。
