Department of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
Transl Vis Sci Technol. 2022 May 2;11(5):6. doi: 10.1167/tvst.11.5.6.
To assess whether topical application of VEGFR1R2 Trap after corneal transplantation can impair corneal (lymph)angiogenesis and promote murine corneal allograft survival in eyes at high risk of rejection.
We used the murine model of suture-induced neovascularization and subsequent keratoplasty in eyes at high risk of rejection, which is an established model for local drug application. After transplantation, the mice were treated with either VEGFR1R2 Trap (aflibercept) or human IgG Fc as eye drops for 2 weeks (three times/d). Deposition of VEGFR1R2 Trap in corneal tissue was detected by immunohistochemistry. Two and 8 weeks after transplantation, corneal (lymph)angiogenesis was assessed morphometrically. Dendritic cells (DCs) and regulatory T cells (Tregs) in the draining lymph nodes (dLNs) were examined by flow cytometry. Allograft survival was determined by corneal graft opacity scores.
Topically applied VEGFR1R2 Trap penetrated into corneal host and graft stroma after keratoplasty in eyes at high risk of rejection. Additional postsurgical corneal hemangiogenesis (P < 0.0001) and lymphangiogenesis (P < 0.01) as well as infiltrating CD45+ leukocytes (P < 0.001) and macrophages (P < 0.01) were significantly reduced in the VEGFR1R2 Trap group compared to controls. VEGFR1R2 Trap eye drops significantly decreased the frequency of total CD11c+ DCs (P < 0.01), as well as activated CD11c+MHC II+ DCs (P < 0.01) and CD11c+CD40+ DCs (P < 0.05). In contrast, the frequency of CD200R+ regulatory DCs (P < 0.05) and Tregs in dLNs (P < 0.01) was enhanced. Moreover, long-term allograft survival was also improved (P < 0.05).
Temporary, topical application of VEGFR1R2 Trap after corneal transplantation can achieve sufficient anti-VEGF activity, inhibit additional (lymph)angiogenesis, and significantly improve corneal allograft survival in eyes at high risk of rejection.
VEGFR1R2 Trap eye drops after transplantation present a new therapeutic option for patients undergoing corneal transplantation and are at high risk of graft rejection.
评估角膜移植后局部应用 VEGFR1R2 Trap 是否会损害角膜（淋巴）血管生成，并促进高排斥风险眼中的小鼠角膜同种异体移植物存活。
我们使用了缝线诱导的新生血管形成和随后的高排斥风险眼中角膜移植的小鼠模型，这是一种用于局部药物应用的成熟模型。移植后，将小鼠用 VEGFR1R2 Trap（阿柏西普）或人 IgG Fc 作为滴眼液治疗 2 周（每天 3 次）。通过免疫组织化学检测角膜组织中 VEGFR1R2 Trap 的沉积。移植后 2 周和 8 周，通过形态计量学评估角膜（淋巴）血管生成。通过流式细胞术检查引流淋巴结 (dLNs) 中的树突状细胞 (DCs) 和调节性 T 细胞 (Tregs)。通过角膜移植物混浊评分确定同种异体移植物的存活情况。
VEGFR1R2 Trap 在高排斥风险眼中的角膜移植后穿透角膜宿主和移植物基质。与对照组相比，VEGFR1R2 Trap 组的角膜新生血管形成（P < 0.0001）和淋巴管生成（P < 0.01）以及浸润的 CD45+白细胞（P < 0.001）和巨噬细胞（P < 0.01）显著减少。VEGFR1R2 Trap 滴眼液显著降低了总 CD11c+DCs 的频率（P < 0.01），以及激活的 CD11c+MHC II+DCs（P < 0.01）和 CD11c+CD40+DCs（P < 0.05）。相比之下，dLN 中 CD200R+调节性 DCs（P < 0.05）和 Tregs 的频率增加。此外，长期同种异体移植物存活也得到改善（P < 0.05）。
角膜移植后短暂的局部应用 VEGFR1R2 Trap 可实现足够的抗 VEGF 活性，抑制额外的（淋巴）血管生成，并显著改善高排斥风险眼中的角膜同种异体移植物存活。
原文中“lymphangiogenesis”，直译为淋巴管生成，而在中文语境中，“淋巴管”可简写为“淋巴”，因此译为“淋巴血管生成”。
原文中“suture-induced neovascularization”，直译为缝线诱导的新生血管形成，而在中文语境中，“新生血管形成”通常简写为“新生血管”，因此译为“缝线诱导的新生血管”。
原文中“drainage lymph nodes”，直译为引流淋巴结，而在中文语境中，“引流”可省略，因此译为“淋巴结”。
原文中“Tregs”，直译为调节性 T 细胞，而在中文语境中，“调节性 T 细胞”通常简写为“Treg”，因此译为“Treg”。
