Myeloid cell function in corneal hem- and lymphangiogenesis

骨髓细胞在角膜血管和淋巴管生成中的功能

• 批准号: 268681468
• 负责人: Professorin Dr. Sabine Eming
• 金额: --
• 依托单位: Klinik für Dermatologie und Venerologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/268681468?language=en
• 关键词: Myeloid; cell; function; corneal; hem

Injury-associated ingrowth of blood and lymphatic vessels into the physiologically avascular cornea significantly impairs visual acuity and mediates diseases like corneal transplant rejection, dry eye disease, and allergy. Macrophages are important mediators of inflammatory corneal hem- and lymphangiogenesis. Yet, the exact mechanisms of blood monocyte recruitment, corneal macrophage activation and the functional consequences of this process for corneal hem-/lymphangiogenesis are not fully understood. In the current funding period we identified distinct functions of macrophages during diverse phases of injury-induced corneal hem- and lymphangiogenesis. In addition, we uncovered a critical role for IL-10 signaling in macrophages regulating the resolution of corneal inflammation via lymphatic vessels after corneal injury. In the next funding period, we are aiming to further characterize the specific regulation and function of myeloid cell subsets in hem- and lymphangiogenesis after corneal tissue damage. Specifically, we will identify the functional role of CX3CR1 in corneal hem- and lymphangiogenesis after acute or chronic injury. Furthermore, we will characterize the contribution of macrophages in the regulation of cornea edema and edema-associated lymphangiogenesis. Together, this work will unravel the precise role of blood monocytes/macrophages recruited to sites of corneal damage and should provide novel immunomodulatory therapies promoting corneal repair or preventing disease.

损伤相关的血管和淋巴管向内生长到生理性无血管角膜中显著损害视力并介导疾病，如角膜移植排斥、干眼病和过敏。巨噬细胞是炎症性角膜出血和淋巴管生成的重要介质。然而，血液单核细胞募集、角膜巨噬细胞活化的确切机制以及该过程对角膜出血/淋巴管生成的功能后果尚未完全了解。在当前的资助期内，我们确定了巨噬细胞在损伤诱导的角膜出血和淋巴管生成的不同阶段的不同功能。此外，我们发现了IL-10信号在巨噬细胞中的关键作用，其在角膜损伤后通过淋巴管调节角膜炎症的消退。在下一个资助期，我们的目标是进一步表征角膜组织损伤后骨髓细胞亚群在血管生成和淋巴管生成中的特异性调节和功能。具体来说，我们将确定CX 3CR 1在急性或慢性损伤后角膜出血和淋巴管生成中的功能作用。此外，我们将表征巨噬细胞在角膜水肿和水肿相关淋巴管生成调节中的作用。总之，这项工作将揭示血液单核细胞/巨噬细胞招募到角膜损伤部位的确切作用，并应提供新的免疫调节疗法，促进角膜修复或预防疾病。