Myeloid cell function in corneal hem- and lymphangiogenesis

损伤相关的血液和淋巴管长入生理性无血管角膜会显著损害视力，并介导角膜移植排斥反应、干眼病和过敏等疾病。巨噬细胞是炎症性角膜内皮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这一过程对角膜内皮/淋巴管生成的功能后果尚不完全清楚。在目前的资助期内，我们发现巨噬细胞在损伤诱导的角膜新生和淋巴管生成的不同阶段具有不同的功能。此外，我们发现巨噬细胞IL-10信号在角膜损伤后通过淋巴管调节角膜炎症消退中的关键作用。在下一个资助期，我们的目标是进一步表征骨髓细胞亚群在角膜组织损伤后hem和淋巴管生成中的具体调控和功能。具体来说，我们将确定CX3CR1在急性或慢性损伤后角膜新生和淋巴管生成中的功能作用。此外，我们将描述巨噬细胞在角膜水肿和水肿相关淋巴管生成的调节中的作用。总之，这项工作将揭示血液单核细胞/巨噬细胞募集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。

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.