Department of Ophthalmology, University Hospital of Cologne, 50937, Cologne, Germany.
Department of Dermatology, University of Cologne, 50937, Cologne, Germany.
Sci Rep. 2019 Jan 22;9(1):308. doi: 10.1038/s41598-018-36526-6.
Macrophages are critical mediators of injury-associated corneal hemangiogenesis (HA) and lymphangiogenesis (LA). Yet, molecular regulators of the hem- and lymphangiogenic potential of corneal wound macrophages are poorly understood. Using two different mouse models of acute (perforating corneal incision injury) and chronic (corneal suture placement model) corneal injury, here we identified distinct functions of early- versus late-phase corneal wound macrophages in corneal HA and LA. Whereas early-phase wound macrophages are essential for initiation and progression of injury-mediated corneal HA and LA, late-phase wound macrophages control maintenance of established corneal lymphatic vessels, but not blood vessels. Furthermore, our findings reveal that the hem- and lymphangiogenic potential of corneal wound macrophages is controlled by the type of the corneal damage. Whereas perforating corneal incision injury induced primarily wound macrophages with lymphangiogenic potential, corneal suture placement provoked wound macrophages with both hem- and lymphangiogenic potential. Our findings highlight a previously unrecognized injury-context dependent role of early- versus late-phase corneal wound macrophages with potential clinical impact on therapy development for sight-threatening corneal neovascular diseases.
巨噬细胞是损伤相关角膜血管生成（HA）和淋巴管生成（LA）的关键介质。然而，角膜伤口巨噬细胞的血管生成和淋巴管生成潜能的分子调节剂知之甚少。在这里，我们使用两种不同的急性（穿孔性角膜切口损伤）和慢性（角膜缝线放置模型）角膜损伤的小鼠模型，鉴定了早期和晚期角膜伤口巨噬细胞在角膜 HA 和 LA 中的不同功能。早期伤口巨噬细胞对于启动和进展损伤介导的角膜 HA 和 LA 是必需的，而晚期伤口巨噬细胞控制已建立的角膜淋巴管的维持，但不控制血管。此外，我们的研究结果表明，角膜伤口巨噬细胞的血管生成和淋巴管生成潜能受角膜损伤类型的控制。穿孔性角膜切口损伤主要诱导具有淋巴管生成潜能的伤口巨噬细胞，而角膜缝线放置则引发具有血管生成和淋巴管生成潜能的伤口巨噬细胞。我们的研究结果强调了早期和晚期角膜伤口巨噬细胞在损伤背景下的以前未被认识到的作用，这可能对治疗威胁视力的角膜新生血管疾病的发展具有潜在的临床影响。
