TY - JOUR
T1 - Eyelid blood vessel and meibomian gland changes in a sclerodermatous chronic GVHD mouse model
AU - Yang, Fan
AU - Hayashi, Isami
AU - Sato, Shinri
AU - Saijo-Ban, Yumiko
AU - Yamane, Mio
AU - Fukui, Masaki
AU - Shimizu, Eisuke
AU - He, Jingliang
AU - Shibata, Shinsuke
AU - Mukai, Shin
AU - Asai, Kazuki
AU - Ogawa, Mamoru
AU - Lan, Yuqing
AU - Zeng, Qingyan
AU - Hirakata, Akito
AU - Tsubota, Kazuo
AU - Ogawa, Yoko
N1 - Funding Information:
The authors thank Dr. Tetsuya Yano and Dr. Hajime Kamijuku for excellent instructions. This study was supported by grants from the Japanese Ministry of Education, Science, Sports, Culture and Technology ( 26462668 , 18K09421 and 21K09752 to Y.O., 19K18855 to I.H., and 26861468 to Y.S.) and from the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project of the Japan Agency for Medical Research and Development (AMED) ( JP18dm0207002 to S.S.)
Publisher Copyright:
© 2021
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - BMT
KW - Eyelid vessel
KW - Fibrotic change
KW - GVHD
KW - MGD
KW - Meibomian gland
KW - Neovasculization
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U2 - 10.1016/j.jtos.2021.10.006
DO - 10.1016/j.jtos.2021.10.006
M3 - Article
AN - SCOPUS:85118899964
SN - 1542-0124
VL - 26
SP - 328
EP - 341
JO - Ocular Surface
JF - Ocular Surface
ER -