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基于化疗的次要匹配小鼠模型中的眼移植物抗宿主病具有角膜(淋)血管生成特征。

Ocular Graft-versus-Host Disease in a Chemotherapy-Based Minor-Mismatch Mouse Model Features Corneal (Lymph-) Angiogenesis.

机构信息

Division of Dry-Eye and Ocular GVHD, Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Hematology, Oncology and Tumorimmunology, Augustenburger Platz 1, 13353 Berlin, Germany.

出版信息

Int J Mol Sci. 2021 Jun 8;22(12):6191. doi: 10.3390/ijms22126191.

Abstract

Ocular graft-versus-host disease (oGVHD) is a fast progressing, autoimmunological disease following hematopoietic stem cell transplantation, leading to severe inflammation of the eye and destruction of the lacrimal functional unit with consecutive sight-threatening consequences. The therapeutic "window of opportunity" is narrow, and current treatment options are limited and often insufficient. To achieve new insights into the pathogenesis and to develop new therapeutic approaches, clinically relevant models of oGVHD are desirable. In this study, the ocular phenotype was described in a murine, chemotherapy-based, minor-mismatch GVHD model mimicking early-onset chronic oGVHD, with corneal epitheliopathy, inflammation of the lacrimal glands, and blepharitis. Additionally, corneal lymphangiogenesis was observed as part of oGVHD pathogenesis for the first time, thus opening up the investigation of lymphangiogenesis as a potential therapeutic and diagnostic tool.

摘要

眼移植物抗宿主病(oGVHD)是造血干细胞移植后一种快速进展的自身免疫性疾病,导致眼睛严重炎症和泪液功能单位破坏,随后出现威胁视力的后果。治疗的“机会之窗”很窄,目前的治疗选择有限,而且往往不够充分。为了深入了解发病机制并开发新的治疗方法,需要具有临床相关性的 oGVHD 模型。在这项研究中,描述了一种基于化疗的、具有微小错配的小鼠 GVHD 模型中的眼部表型,该模型模拟了早期慢性 oGVHD,表现为角膜上皮病、泪腺炎症和睑缘炎。此外,首次观察到角膜淋巴管生成是 oGVHD 发病机制的一部分,从而为淋巴管生成作为一种潜在的治疗和诊断工具开辟了研究途径。

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