Department of Ophthalmology, University of Cologne, Cologne, Germany.
Department of Ophthalmology, Hue College of Medicine and Pharmacy, Hue University, Hue, Vietnam.
Am J Transplant. 2018 Dec;18(12):2873-2884. doi: 10.1111/ajt.14874. Epub 2018 May 26.
Immunologic graft rejection is the main complication after corneal transplant into pathologically prevascularized so-called high-risk eyes. The aim of this study was to evaluate whether ultraviolet (UV) light crosslinking can regress pathologic corneal blood and lymphatic vessels and thereby improve subsequent graft survival. Using the murine model of suture-induced corneal neovascularization, we found that corneal crosslinking with UVA light and riboflavin regressed both preexisting blood and lymphatic vessels significantly via induction of apoptosis in vascular endothelial cells. In addition, macrophages and CD45 cell counts were significantly reduced. Consistently, corneal crosslinking reduced keratocyte density and corneal thickness without affecting corneal nonvascular endothelial cells, iris, and lens depending on the crosslinking duration. Furthermore, using the murine model of corneal transplant, long-term graft survival was significantly promoted (P < .05) and CD4 CD25 FoxP3 T regulatory cells were upregulated (P < .01) in high-risk eyes preoperatively treated with crosslinking. Our results suggest UV light crosslinking as a novel method to regress both pathologic corneal blood and lymphatic vessels and to reduce CD45 inflammatory cells. Furthermore, this study demonstrates for the first time that preoperative corneal crosslinking in prevascularized high-risk eyes can significantly improve subsequent graft survival and may become a promising novel therapy in the clinic.
免疫移植物排斥反应是病理性血管化所谓高危眼角膜移植后的主要并发症。本研究旨在评估紫外线(UV)光交联是否可以使病理性角膜血管和淋巴管退化,从而提高随后的移植物存活率。使用缝线诱导的角膜新生血管形成的小鼠模型,我们发现 UVA 光和核黄素角膜交联通过诱导血管内皮细胞凋亡,显著消退了预先存在的血液和淋巴管。此外,巨噬细胞和 CD45 细胞计数明显减少。一致地,角膜交联减少了角膜成纤维细胞密度和角膜厚度,而不影响角膜非血管内皮细胞、虹膜和晶状体,这取决于交联持续时间。此外,使用角膜移植的小鼠模型,术前用交联处理的高危眼的长期移植物存活率显著提高(P<.05),并且 CD4 CD25 FoxP3 T 调节性细胞上调(P<.01)。我们的结果表明,UV 光交联是一种消退病理性角膜血管和淋巴管并减少 CD45 炎症细胞的新方法。此外,本研究首次证明,在血管化高危眼中进行术前角膜交联可以显著提高随后的移植物存活率,并可能成为临床有前途的新疗法。