Fukuhara Junichi, Kase Satoru, Ohashi Tsutomu, Ando Ryo, Dong Zhenyu, Noda Kousuke, Ohguchi Takeshi, Kanda Atsuhiro, Ishida Susumu
Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Nishi 7, Kita 15, Sapporo 060-8638, Japan.
Histochem Cell Biol. 2013 Feb;139(2):381-9. doi: 10.1007/s00418-012-1019-z. Epub 2012 Aug 23.
Vascular endothelial growth factor C (VEGF-C) and its receptor VEGFR-3 mediate lymphangiogenesis. In this study, we analyzed the expression of VEGF-C and VEGFR-3 as well as lymphatic vessels in the pterygium and normal conjunctiva of humans. Fifteen primary nasal pterygia and three normal bulbar conjunctivas, surgically removed, were examined in this study. The lymphatic vessel density (LVD) and blood vessel density were determined by the immunolabeling of D2-40 and CD31, markers for lymphatic and blood vessels, respectively. VEGF-C and VEGFR-3 expression in pterygial and conjunctival tissue proteins was detected by Western blotting and were evaluated using immunohistochemistry. The LVD was significantly higher in the pterygium than normal conjunctiva (p < 0.05). Western blot demonstrated high-level expression of VEGF-C and VEGFR-3 in the pterygium compared with normal conjunctiva. VEGF-C immunoreactivity was detected in the cytoplasm of pterygial and normal conjunctival epithelial cells. The number of VEGF-C-immunopositive cells in pterygial epithelial cells was significantly higher than in normal conjunctival cells (p < 0.05). VEGFR-3 immunoreactivity was localized in the D2-40-positive lymphatic endothelial cells. The present findings suggest the potential role of VEGF-C in the pathogenesis and development of a pterygium through lymphangiogenesis and the VEGF-C/VEGFR-3 pathway as a novel therapeutic target for the human pterygium.
血管内皮生长因子C（VEGF-C）及其受体VEGFR-3介导淋巴管生成。在本研究中，我们分析了VEGF-C和VEGFR-3的表达以及人类翼状胬肉和正常结膜中的淋巴管。本研究检查了手术切除的15例原发性鼻侧翼状胬肉和3例正常球结膜。通过分别用淋巴管和血管的标志物D2-40和CD31进行免疫标记来测定淋巴管密度（LVD）和血管密度。通过蛋白质印迹法检测翼状胬肉和结膜组织蛋白中VEGF-C和VEGFR-3的表达，并使用免疫组织化学进行评估。翼状胬肉中的LVD显著高于正常结膜（p<0.05）。蛋白质印迹显示，与正常结膜相比，翼状胬肉中VEGF-C和VEGFR-3表达水平较高。在翼状胬肉和正常结膜上皮细胞的细胞质中检测到VEGF-C免疫反应性。翼状胬肉上皮细胞中VEGF-C免疫阳性细胞的数量显著高于正常结膜细胞（p<0.05）。VEGFR-3免疫反应性定位于D2-40阳性的淋巴管内皮细胞中。目前的研究结果表明，VEGF-C通过淋巴管生成和VEGF-C/VEGFR-3途径在翼状胬肉的发病机制和发展中具有潜在作用，可作为人类翼状胬肉的新治疗靶点。
