Department of Ophthalmology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Invest Ophthalmol Vis Sci. 2012 Dec 19;53(13):8458-71. doi: 10.1167/iovs.12-10408.
This study sought to determine whether a Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-specific morpholino (MO) could decrease neovascularization, thereby enhancing murine cornea transplant survival, and if this effect is synergistic with steroid therapy.
Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the VEGFR1_MO, STD MO and PBS groups following subconjunctival injection in mice that underwent normal risk penetrating keratoplasty (NR PK) and high-risk penetrating keratoplasty (HR PK). Graft survival, corneal neovascularization, and corneal lymphangiogenesis in groups treated with both VEGFR1_MO and steroid therapy were also analyzed in HR PK.
In NR PK, the VEGFR1_MO decreased angiogenesis, lymphangiogenesis, and increased graft survival compared with the PBS group (P = 0.055, P = 0.003, P = 0.043, respectively). In HR PK, VEGFR1_MO decreased angiogenesis, lymphangiogenesis, and increased graft survival compared with the STD MO (P = 0.000, P = 0.000, P = 0.029, respectively) and PBS groups (P = 0.004, P = 0.002, P = 0.024). In HR PK, when the VEGFR1_MO was combined with steroid therapy, a significant increase in graft survival was seen compared with steroid treatment alone (P = 0.045). The 2-month graft survival rate for HR PK was 27% in the combination group compared with 0% in the triamcinolone only group.
VEGFR1_MO decreased angiogenesis and lymphangiogenesis, resulting in increased graft survival in both NR PK and HR PK. This beneficial effect is synergistically enhanced with steroid treatment in HR PK.
本研究旨在确定血管内皮生长因子受体 1（VEGFR1）特异性的 morpholino（MO）是否能减少新生血管形成，从而提高小鼠角膜移植的存活率，以及这种效果是否与类固醇治疗具有协同作用。
在进行正常风险穿透性角膜移植（NR PK）和高风险穿透性角膜移植（HR PK）的小鼠中，通过结膜下注射，比较 VEGFR1_MO、STD MO 和 PBS 组之间的移植物存活率、角膜新生血管形成和角膜淋巴管生成。还分析了 HR PK 中同时使用 VEGFR1_MO 和类固醇治疗的各组的移植物存活率、角膜新生血管形成和角膜淋巴管生成。
在 NR PK 中，与 PBS 组相比，VEGFR1_MO 降低了血管生成、淋巴管生成，并提高了移植物存活率（P = 0.055、P = 0.003、P = 0.043）。在 HR PK 中，与 STD MO 组和 PBS 组相比，VEGFR1_MO 降低了血管生成、淋巴管生成，并提高了移植物存活率（P = 0.000、P = 0.000、P = 0.029）。在 HR PK 中，当 VEGFR1_MO 与类固醇治疗联合使用时，与单独使用类固醇治疗相比，移植物存活率显著增加（P = 0.045）。在 HR PK 中，联合组的 2 个月移植物存活率为 27%，而单独使用曲安奈德组为 0%。
VEGFR1_MO 降低了血管生成和淋巴管生成，从而提高了 NR PK 和 HR PK 中的移植物存活率。这种有益的效果在 HR PK 中与类固醇治疗具有协同作用。
