Eyelid blood vessel and meibomian gland changes in a sclerodermatous chronic GVHD mouse model,The Ocular Surface

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Eyelid blood vessel and meibomian gland changes in a sclerodermatous chronic GVHD mouse model
The Ocular Surface ( IF 5.9 ) Pub Date : 2021-10-26 , DOI: 10.1016/j.jtos.2021.10.006
Fan Yang ₁ , Isami Hayashi ₂ , Shinri Sato ₃ , Yumiko Saijo-Ban ₃ , Mio Yamane ₃ , Masaki Fukui ₃ , Eisuke Shimizu ₃ , Jingliang He ₄ , Shinsuke Shibata ₅ , Shin Mukai ₆ , Kazuki Asai ₃ , Mamoru Ogawa ₃ , Yuqing Lan ₇ , Qingyan Zeng ₈ , Akito Hirakata ₉ , Kazuo Tsubota ₁₀ , Yoko Ogawa ₃

Affiliation

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.
Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan.
Eye Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Electron Microscope Laboratory, Keio University School of Medicine, Tokyo, Japan.
Center for Interdisciplinary Cardiovascular Sciences, Brigham and Women's Hospital, Harvard Medical School, Massachusetts, USA.
Department of Ophthalmology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Aier Eye Hosoital of Wuhan University, Wuhan, Hubei province, China.
Department of Ophthalmology, Kyorin University, School of Medicine, Tokyo, Japan.
Department of Ophthalmology, Keio University, School of Medicine, Tokyo, Japan; Tsubota Laboratory, Inc., Tokyo, Japan.

Purpose

To investigate pathological changes in blood vessels and meibomian glands (MGs) in the eyelids of sclerodermatous chronic graft-versus-host disease (cGVHD) model mice.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

硬皮病慢性 GVHD 小鼠模型眼睑血管和睑板腺的变化

目的

研究硬皮病慢性移植物抗宿主病 (cGVHD) 模型小鼠眼睑血管和睑板腺 (MG) 的病理变化。

方法

我们使用了已建立的主要组织相容性复合物相容性、多个次要组织相容性抗原不匹配的硬皮病 cGVHD 小鼠模型。通过组织病理学、免疫和透射电子显微镜评估来自同种异体骨髓移植(allo-BMT) 受体小鼠和同基因骨髓移植 (syn-BMT) 受体小鼠的眼睑血管和 MG 。通过流式细胞术检查接受者的外周血样本。

结果

Allo-BMT 样本显示扩张、扭曲和分支的血管以及眼睑中收缩的 MG；在外周 MG 区域显示 VEGFR2 (p = 0.029)、CD133 (p = 0.016)、GFP (p = 0.006) 和 α-SMA (p = 0.029) 的表达显着更高；与 syn-BMT 样本相比，显示内皮损伤和激活、纤维化变化和免疫细胞浸润到 MGs 中。在同种异体 BMT 和同种 BMT 样本中观察到的Ki-67⁺细胞少于野生型样本 (p = 0.030)。allo-BMT 样本与 syn-BMT 样本相比，超微结构变化包括内皮损伤和激活、成纤维细胞激活、粒细胞脱颗粒、免疫细胞浸润到 MGs 以及 MG 基底细胞坏死、凋亡。