Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
Invest Ophthalmol Vis Sci. 2012 Mar 9;53(3):1244-50. doi: 10.1167/iovs.11-8668. Print 2012 Mar.
To investigate the role of anti-vascular endothelial growth factor (VEGF)-C therapy in corneal graft survival and concomitant suppression of hem- and lymph-angiogenesis.
Corneal suture model in BALB/c mice was placed and immunohistochemical staining was performed with CD31/PECAM-1 and LYVE-1 to quantify the level of blood and lymphatic vessels. Corneal transplants were done in BALB/c mice from C57BL/6 mice donors; grafts were subsequently scored for opacity. VEGF-C was blocked in the angiogenesis and transplant model using neutralizing monoclonal anti-VEGF-C (VGX-100) by intraperitoneal injection. To determine the function of VEGF-C in maturation of antigen-presenting cells (APCs), bone marrow-derived dendritic cells were generated and matured in the presence or absence of VEGF-C.
VEGF-C expression was demonstrated to be markedly upregulated in corneal graft rejection. VEGF-C blockade, through administration of a VEGF-C blocking monoclonal antibody, suppresses corneal angiogenic responses, inhibits trafficking and maturation of APCs, and significantly improves allotransplant survival.
These data suggest VEGF-C as a potentially important target in corneal transplant pharmacotherapy and immunobiology.
研究抗血管内皮生长因子（VEGF）-C 治疗在角膜移植物存活和伴随的抑制血管生成和淋巴管生成中的作用。
在 BALB/c 小鼠中放置角膜缝线模型，并使用 CD31/PECAM-1 和 LYVE-1 进行免疫组织化学染色，以定量血液和淋巴管的水平。将 C57BL/6 小鼠供体的角膜移植到 BALB/c 小鼠中；随后对混浊度进行评分。通过腹腔内注射中和单克隆抗 VEGF-C（VGX-100）在血管生成和移植模型中阻断 VEGF-C。为了确定 VEGF-C 在抗原呈递细胞（APC）成熟中的功能，生成并在存在或不存在 VEGF-C 的情况下成熟骨髓来源的树突状细胞。
VEGF-C 的表达在角膜移植物排斥中明显上调。通过给予 VEGF-C 阻断单克隆抗体，VEGF-C 阻断抑制了角膜血管生成反应，抑制了 APC 的迁移和成熟，并显著提高了同种异体移植物的存活率。
这些数据表明 VEGF-C 是角膜移植药物治疗和免疫生物学中一个潜在的重要靶点。
