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色素上皮衍生因子在正常成年大鼠眼及实验性脉络膜新生血管中的表达

Expression of pigment epithelium-derived factor in normal adult rat eye and experimental choroidal neovascularization.

作者信息

Ogata Nahoko, Wada Mitsumasa, Otsuji Tsuyoshi, Jo Nobuo, Tombran-Tink Joyce, Matsumura Miyo

机构信息

Department of Ophthalmology, Kansai Medical University, Moriguchi, Osaka, Japan.

出版信息

Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1168-75.

Abstract

PURPOSE

Pigment epithelium-derived factor (PEDF) is a protein produced by the retinal pigment epithelial (RPE) cells. Recent studies have implicated PEDF in activities that are inhibitory to angiogenesis. In this study, the expression of PEDF was investigated in normal rat eyes and in eyes with experimentally induced choroidal neovascularization and compared with the expression of vascular endothelial growth factor (VEGF).

METHODS

Choroidal neovascularization was induced by laser photocoagulation in rat eyes. At intervals of up to 2 weeks after photocoagulation, the eyes were removed and prepared for in situ hybridization and immunohistochemical study. In situ hybridization was performed with digoxigenin-labeled PEDF riboprobes. Protein expression of PEDF and VEGF was studied immunohistochemically.

RESULTS

In normal adult rat eyes, PEDF mRNA was observed mainly in the corneal epithelial and endothelial cells, lens epithelial cells, ciliary epithelial cells, retinal ganglion cells, and the RPE cells. During the development of choroidal neovascularization, PEDF mRNA, PEDF protein, and VEGF protein were strongly detected in many cells within the laser lesions at 3 days after photocoagulation, after which levels gradually declined. However, PEDF was still expressed in the RPE cells that proliferated and covered the neovascular tissues at 2 weeks, whereas VEGF protein was weakly expressed in endothelial cells in choroidal neovascularization.

CONCLUSIONS

PEDF is expressed in different cell types of normal rat eyes. The expression of PEDF was detected in the choroidal neovascular tissues induced by photocoagulation, and these findings suggest that PEDF may modulate the process of choroidal neovascularization.

摘要

目的

色素上皮衍生因子(PEDF)是一种由视网膜色素上皮(RPE)细胞产生的蛋白质。最近的研究表明PEDF参与抑制血管生成的活动。在本研究中,研究了PEDF在正常大鼠眼中以及实验性诱导脉络膜新生血管形成的眼中的表达,并与血管内皮生长因子(VEGF)的表达进行比较。

方法

通过激光光凝诱导大鼠眼脉络膜新生血管形成。在光凝后长达2周的时间间隔内,取出眼睛并制备用于原位杂交和免疫组织化学研究。用洋地黄毒苷标记的PEDF核糖探针进行原位杂交。通过免疫组织化学研究PEDF和VEGF的蛋白表达。

结果

在正常成年大鼠眼中,PEDF mRNA主要在角膜上皮和内皮细胞、晶状体上皮细胞、睫状上皮细胞、视网膜神经节细胞和RPE细胞中观察到。在脉络膜新生血管形成过程中,光凝后3天在激光损伤内的许多细胞中强烈检测到PEDF mRNA、PEDF蛋白和VEGF蛋白,此后水平逐渐下降。然而,在2周时增殖并覆盖新生血管组织的RPE细胞中仍表达PEDF,而脉络膜新生血管中的内皮细胞中VEGF蛋白表达较弱。

结论

PEDF在正常大鼠眼的不同细胞类型中表达。在光凝诱导的脉络膜新生血管组织中检测到PEDF的表达,这些发现表明PEDF可能调节脉络膜新生血管形成的过程。

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