Eyelid blood vessel and meibomian gland changes in a sclerodermatous chronic GVHD mouse model

Fan Yang, Isami Hayashi, Shinri Sato, Yumiko Saijo-Ban, Mio Yamane, Masaki Fukui, Eisuke Shimizu, Jingliang He, Shinsuke Shibata, Shin Mukai, Kazuki Asai, Mamoru Ogawa, Yuqing Lan, Qingyan Zeng, Akito Hirakata, Kazuo Tsubota, Yoko Ogawa

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalOcular Surface
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • BMT
  • Eyelid vessel
  • Fibrotic change
  • GVHD
  • MGD
  • Meibomian gland
  • Neovasculization

ASJC Scopus subject areas

  • Ophthalmology

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