Myeloid cell function in corneal hem- and lymphangiogenesis

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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.