Hollborn Margrit, Faude Frank, Wiedemann Peter, Kohen Leon
Department of Ophthalmology, University of Leipzig, Liebigstrasse 10-14, 04103 Leipzig, Germany.
Graefes Arch Clin Exp Ophthalmol. 2003 May;241(5):439-46. doi: 10.1007/s00417-003-0664-2. Epub 2003 Apr 16.
Retinal detachment is often accompanied by proliferation and migration of retinal cells and by increased synthesis of structural proteins, known as proliferative vitreoretinopathy (PVR). Herein we investigate the messenger RNA (mRNA) expression of proto-oncogenes responsible for cell proliferation and of structural proteins that have a role in membrane formation.
Retinal samples were obtained from patients undergoing vitreoretinal surgery for the treatment of retinal detachment complicated by PVR. Normal human control retinas were obtained from cornea donors. The mRNA expression of the proto-oncogenes c- myc, c- fos and the proliferation marker Ki67, as well as of collagen type III and type IV, were investigated using the ribonuclease protection assay.
Ki67 mRNA expression was not detectable in either sample type, but c- fos and c- myc mRNA expression was found in normal and PVR retinas. Whereas the expression of c- myc showed a marginal increase, the up-regulation in c- fos expression was strongly significant (5.07-fold). The mRNA of collagen type III was detectable at widely varying levels in all the PVR retinas but was found in only 2 of the 16 analysed normal samples. Collagen type IV mRNA was expressed in both PVR and control samples but was higher (2.21-fold) in the PVR retinas.
These results indicate that an up-regulation of the proto-oncogene c- fos occurs in human PVR retinas. An increase in mRNA expression of collagen types III and IV takes place simultaneously. These changes in mRNA expression appear to be mainly connected to the initiation of cell proliferation, dedifferentiation and formation of tractional membranes.
视网膜脱离常伴有视网膜细胞的增殖和迁移以及结构蛋白合成增加,即增殖性玻璃体视网膜病变(PVR)。在此,我们研究负责细胞增殖的原癌基因以及在膜形成中起作用的结构蛋白的信使核糖核酸(mRNA)表达。
视网膜样本取自接受玻璃体视网膜手术治疗并发PVR的视网膜脱离患者。正常人类对照视网膜取自角膜捐献者。使用核糖核酸酶保护试验研究原癌基因c-myc、c-fos和增殖标志物Ki67以及III型和IV型胶原的mRNA表达。
在两种样本类型中均未检测到Ki67 mRNA表达,但在正常和PVR视网膜中发现了c-fos和c-myc mRNA表达。虽然c-myc的表达略有增加,但c-fos表达的上调非常显著(5.07倍)。III型胶原mRNA在所有PVR视网膜中的表达水平差异很大,但在16个分析的正常样本中仅在2个样本中发现。IV型胶原mRNA在PVR和对照样本中均有表达,但在PVR视网膜中更高(2.21倍)。
这些结果表明人类PVR视网膜中原癌基因c-fos上调。III型和IV型胶原的mRNA表达同时增加。这些mRNA表达的变化似乎主要与细胞增殖、去分化和牵拉性膜的形成有关。