Martin Gottfried, Schlunck Günther, Hansen Lutz L, Agostini Hansjürgen T
Universitaets-Augenklinik Freiburg, Killianstrasse 5, 79106, Freiburg, Germany.
Graefes Arch Clin Exp Ophthalmol. 2004 Apr;242(4):321-6. doi: 10.1007/s00417-003-0838-y. Epub 2004 Jan 14.
Choroidal neovascularization (CNV) causes loss of vision in age-related macular degeneration (AMD). In CNV, choroidal capillaries penetrate Bruch's membrane and the retinal pigment epithelium (RPE). Angiogenic factors produced by RPE cells are suspected as major contributors to CNV development. We therefore studied the differential expression of angioregulatory factors in normal and CNV-derived RPE.
Cultures of normal (ARPE-19) and CNV-derived RPE (CNV-RPE) were compared by quantitative PCR. Differential expression was verified on the protein level by immunohistochemistry in tissue samples.
The angioregulatory factors VEGF-A, VEGF-B, VEGF-C, Angiopoietin-1 (Ang-1) and Angiopoietin-2, Semaphorin-3A, PEDF, HIF-1, FGF-2, and the receptors VEGF-R2, Neuropilin-1 and Neuropilin-2 were detected in both, ARPE-19 and CNV-RPE. Transcription of PEDF, FGF-2, Neuropilin-2, Ang-1 and Ang-2 was significantly upregulated in CNV-RPE. EphA7, VEGF-R1 and leptin were transcribed exclusively in CNV-RPE and Eph-A7 and VEGF-R1 proteins were present exclusively in CNV specimens.
A set of common factors controlling angiogenesis was detected in both, ARPE-19 cells and CNV-RPE cells. Surprisingly, PEDF and other factors inhibiting angiogenesis are strongly upregulated in CNV-RPE; thus, at least in later stages, the RPE has a potential to control angiogenesis in age-related macular degeneration.
脉络膜新生血管（CNV）可导致年龄相关性黄斑变性（AMD）患者视力丧失。在CNV中，脉络膜毛细血管穿透布鲁赫膜和视网膜色素上皮（RPE）。RPE细胞产生的血管生成因子被怀疑是CNV发展的主要促成因素。因此，我们研究了正常和CNV来源的RPE中血管调节因子的差异表达。
通过定量PCR比较正常（ARPE-19）和CNV来源的RPE（CNV-RPE）的培养物。通过组织样本中的免疫组织化学在蛋白质水平上验证差异表达。
在ARPE-19和CNV-RPE中均检测到血管调节因子VEGF-A、VEGF-B、VEGF-C、血管生成素-1（Ang-1）和血管生成素-2、信号素-3A、PEDF、HIF-1、FGF-2以及受体VEGF-R2、神经纤毛蛋白-1和神经纤毛蛋白-2。PEDF、FGF-2、神经纤毛蛋白-2、Ang-1和Ang-2在CNV-RPE中的转录显著上调。EphA7、VEGF-R1和瘦素仅在CNV-RPE中转录，而Eph-A7和VEGF-R1蛋白仅存在于CNV标本中。
在ARPE-19细胞和CNV-RPE细胞中均检测到一组控制血管生成的共同因子。令人惊讶的是，PEDF和其他抑制血管生成的因子在CNV-RPE中强烈上调；因此，至少在后期阶段，RPE有潜力控制年龄相关性黄斑变性中的血管生成。
