Aims Pathological neovascularisation of the host bed and the transplant itself is the main risk factor for graft rejection after corneal transplantation. This study aims to prevent this process by preincubation of the corneal donor tissue ex vivo with an antivascular endothelial growth factor (VEGF) cytokine trap blocking additional postsurgical hemangiogenesis and lymphangiogenesis to promote high-risk graft survival. Methods The donor tissue was preincubated with a VEGFR1R2 cytokine trap for 24 hours prior to murine high-risk corneal transplantation (human IgG Fc was used as the control). The distribution of VEGFR1R2 Trap in the cornea was investigated by immunohistochemistry. Corneas were excised to quantify the blood vessels (BVs) and lymphatic vessels (LVs) and draining lymph nodes (dLNs) were harvested to analyse the phenotype of dendritic cells (DCs) and T cells at week 1, 2 and 8 post-transplantation. Graft survival was compared between preincubation with VEGFR1R2 Trap and human IgG Fc in high-risk recipients. Results VEGFR1R2 Trap was present in the graft for at least 2 weeks after surgery and additionally diffused into the corneal recipient. BVs, LVs and macrophages in the whole cornea were significantly decreased 1-week and 2-week post-transplantation (p<0.05). In dLNs the frequency of CD11c+DCs was significantly reduced, whereas CD200R+ regulatory DCs were significantly increased after keratoplasty (p<0.05). Furthermore, long-term high-risk graft survival was significantly improved (p<0.01). Conclusions Preincubation of corneal donor tissue with a VEGFR1R2 cytokine trap can significantly promote subsequent high-risk corneal transplant survival and thereby opens new treatment avenues for high-risk corneal transplantation. Data are available on reasonable request. Data are available on reasonable request by felix.bock@uk-koeln.de.

中文翻译：

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供体组织与 VEGF 细胞因子陷阱的预孵育可促进随后的高风险角膜移植存活

目的宿主床和移植物本身的病理性新生血管形成是角膜移植后移植物排斥的主要危险因素。本研究旨在通过体外预孵育角膜供体组织与抗血管内皮生长因子 (VEGF) 细胞因子陷阱阻止额外的术后血管生成和淋巴管生成来防止这一过程，以促进高风险移植物存活。方法 供体组织在小鼠高危角膜移植前用 VEGFR1R2 细胞因子捕集器预孵育 24 小时（人 IgG Fc 用作对照）。通过免疫组织化学研究角膜中 VEGFR1R2 Trap 的分布。切除角膜以量化血管 (BV) 和淋巴管 (LV)，并收获引流淋巴结 (dLN) 以分析移植后第 1、2 和 8 周树突状细胞 (DC) 和 T 细胞的表型。在高危受体中比较了用 VEGFR1R2 Trap 和人 IgG Fc 预孵育的移植物存活率。结果 VEGFR1R2 Trap 在手术后至少 2 周存在于移植物中，并且另外扩散到角膜受体中。移植后 1 周和 2 周，整个角膜中的 BV、LV 和巨噬细胞显着减少 (p<0.05)。在 dLNs 中，CD11c+DCs 的频率显着降低，而 CD200R+调节性 DCs 在角膜移植术后显着增加（p<0.05）。此外，长期高危移植物存活率显着提高（p<0.01）。结论 角膜供体组织与 VEGFR1R2 细胞因子捕获剂的预孵育可显着促进后续高危角膜移植的存活，从而为高危角膜移植开辟新的治疗途径。可根据合理要求提供数据。数据可通过 felix.bock@uk-koeln.de 合理要求获得。