CCR2(−) and CCR2(+) corneal macrophages exhibit distinct characteristics and balance inflammatory responses after epithelial abrasion

Macrophages are distributed throughout the body and are crucial for the restoration of damaged tissues. However, their characteristics in the cornea and roles in the repair of corneal injures are unclear. Here we show that corneal macrophages can be classified as CCR2(−) macrophages, which already exist in the cornea at embryonic day 12.5 (E12.5) and are similar to yolk sac-derived macrophages, microglia, in phenotype and gene expression, and CCR2(+) macrophages, which do not appear in the cornea until E17.5. At a steady state, CCR2(−) corneal macrophages have local proliferation capacity and are rarely affected by monocytes; however, following corneal epithelial abrasion, most CCR2(−) corneal macrophages are replaced by monocytes. In contrast, CCR2(+) macrophages are repopulated by monocytes under both a steady-state condition and following corneal wounding. Depletion of CCR2(+) macrophages decreases corneal inflammation after epithelial abrasion, whereas depletion of CCR2(−) macrophages increases inflammation of the injured cornea. Loss of either cell type results in a delay in corneal healing. These data indicate that there are two unique macrophage populations present in the cornea, both of which participate in corneal wound healing by balancing the inflammatory response.