Ocular Surface and Tear Film Characteristics in a Sclerodermatous Chronic Graft-Versus-Host Disease Mouse Model

Jingliang He, Mio Yamane, Shinsuke Shibata, Masaki Fukui, Eisuke Shimizu, Tetsuya Yano, Shin Mukai, Yutaka Kawakami, Shaowei Li, Kazuo Tsubota, Yoko Ogawa

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

PURPOSE: To report the characteristics of the ocular surface in a previously established sclerodermatous chronic graft-versus-host disease (cGVHD) mouse model.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)486-494
Number of pages9
JournalCornea
Volume37
Issue number4
DOIs
Publication statusPublished - 2018 Apr 1

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Graft vs Host Disease
Tears
Conjunctiva
Eyelids
Microvilli
Eye Manifestations
Goblet Cells
Electron Microscopy
Flow Cytometry
Fibrosis
Immunohistochemistry
Body Weight
Staining and Labeling
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Ocular Surface and Tear Film Characteristics in a Sclerodermatous Chronic Graft-Versus-Host Disease Mouse Model. / He, Jingliang; Yamane, Mio; Shibata, Shinsuke; Fukui, Masaki; Shimizu, Eisuke; Yano, Tetsuya; Mukai, Shin; Kawakami, Yutaka; Li, Shaowei; Tsubota, Kazuo; Ogawa, Yoko.

In: Cornea, Vol. 37, No. 4, 01.04.2018, p. 486-494.

Research output: Contribution to journalArticle

He, J, Yamane, M, Shibata, S, Fukui, M, Shimizu, E, Yano, T, Mukai, S, Kawakami, Y, Li, S, Tsubota, K & Ogawa, Y 2018, 'Ocular Surface and Tear Film Characteristics in a Sclerodermatous Chronic Graft-Versus-Host Disease Mouse Model', Cornea, vol. 37, no. 4, pp. 486-494. https://doi.org/10.1097/ICO.0000000000001487
He, Jingliang ; Yamane, Mio ; Shibata, Shinsuke ; Fukui, Masaki ; Shimizu, Eisuke ; Yano, Tetsuya ; Mukai, Shin ; Kawakami, Yutaka ; Li, Shaowei ; Tsubota, Kazuo ; Ogawa, Yoko. / Ocular Surface and Tear Film Characteristics in a Sclerodermatous Chronic Graft-Versus-Host Disease Mouse Model. In: Cornea. 2018 ; Vol. 37, No. 4. pp. 486-494.
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AU - Fukui, Masaki

AU - Shimizu, Eisuke

AU - Yano, Tetsuya

AU - Mukai, Shin

AU - Kawakami, Yutaka

AU - Li, Shaowei

AU - Tsubota, Kazuo

AU - Ogawa, Yoko

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N2 - PURPOSE: To report the characteristics of the ocular surface in a previously established sclerodermatous chronic graft-versus-host disease (cGVHD) mouse model.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

AB - PURPOSE: To report the characteristics of the ocular surface in a previously established sclerodermatous chronic graft-versus-host disease (cGVHD) mouse model.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.

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