Hou Yanhong, Le Viet Nhat Hung, Clahsen Thomas, Schneider Ann-Charlott, Bock Felix, Cursiefen Claus
Department of Ophthalmology, University of Cologne, Germany.
Center for Molecular Medicine Cologne, University of Cologne, Germany.
Invest Ophthalmol Vis Sci. 2017 Nov 1;58(13):5862-5869. doi: 10.1167/iovs.17-22904.
Pathologic corneal (lymph) angiogenesis is a known risk factor for immune-mediated allograft rejections after corneal transplantation. However, there is no established treatment to regress pre-existing pathological corneal blood and lymphatic vessels. This study assessed the possibility to regress both vessel types by photodynamic therapy (PDT) after intravenous (i.v.) verteporfin injection, the influence of timing of PDT after verteporfin injection, and the effect on graft survival in high-risk keratoplasty.
BALB/c mice were used for suture-induced inflammatory corneal neovascularization to induce combined hem- and lymphangiogenesis. The treated group received PDT 3 minutes, 1 hour, and 24 hours after an i.v. verteporfin injection (control group: phosphate buffered saline). Corneal flatmounts were excised 3 days, 1 week, and 2 weeks after corneal PDT and stained with cluster of differentiation 31 (CD31) and lymphatic vessel endothelial hyaluronan receptor 1 antibodies (LYVE-1) to quantify hem- and lymphangiogenesis. Graft survival rates were compared between high-risk recipients with and without preoperative PDT.
Corneal blood vessels were significantly reduced when PDT was performed 3 minutes after i.v. verteporfin injection, whereas lymphatic vessels showed no significant difference. Both blood and lymphatic vessels were regressed when PDT was performed 1 hour or 24 hours after i.v. verteporfin application. Long-term allograft survival increased significantly in PDT-pretreated eyes when compared with controls.
PDT after i.v. verteporfin injection can selectively regress pre-existing corneal blood vessels or both blood and lymphatic vessels depending on the timing of PDT after verteporfin injection. The pretreatment of recipients with PDT and i.v. verteporfin might be a promising new method to improve graft survival in high-risk eyes.
病理性角膜（淋巴）血管生成是角膜移植后免疫介导的同种异体移植排斥反应的已知危险因素。然而，目前尚无已确立的治疗方法可使已存在的病理性角膜血管和淋巴管消退。本研究评估了静脉注射维替泊芬后通过光动力疗法（PDT）使两种血管类型消退的可能性、维替泊芬注射后PDT时间的影响以及对高危角膜移植中移植物存活的影响。
使用BALB/c小鼠通过缝线诱导炎性角膜新生血管形成以诱导血液和淋巴管生成。治疗组在静脉注射维替泊芬后3分钟、1小时和24小时接受PDT（对照组：磷酸盐缓冲盐水）。角膜光镜标本在角膜PDT后3天、1周和2周切除，并用分化簇31（CD31）和淋巴管内皮透明质酸受体1抗体（LYVE-1）染色以量化血液和淋巴管生成。比较术前接受和未接受PDT的高危受者的移植物存活率。
静脉注射维替泊芬后3分钟进行PDT时，角膜血管显著减少，而淋巴管无显著差异。静脉注射维替泊芬后1小时或24小时进行PDT时，血液和淋巴管均消退。与对照组相比，PDT预处理的眼睛长期同种异体移植物存活率显著提高。
静脉注射维替泊芬后进行PDT可根据维替泊芬注射后PDT的时间选择性地使已存在的角膜血管或血液和淋巴管均消退。用PDT和静脉注射维替泊芬对受者进行预处理可能是提高高危眼移植物存活率的一种有前景的新方法。
