Pena J D, Roy S, Hernandez M R
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA.
Matrix Biol. 1996 Nov;15(5):323-30. doi: 10.1016/s0945-053x(96)90135-3.
Elastic fibers are a major component of the extracellular matrix in the optic nerve head (ONH) and undergo marked morphological changes during primary open angle glaucoma (POAG). Previous findings indicated that there is reactivation of tropoelastin mRNA synthesis in glaucoma. In this study, we sought to determine the alternative splicing pattern of tropoelastin in the human optic nerve head and in cultured laminar astrocytes. Furthermore, we compared the alternative splicing pattern of normal elastogenesis with that of reactivation of elastin synthesis in patients with primary open angle glaucoma. Our results demonstrate that exons 23 and 32 of tropoelastin are alternatively spliced in the normal ONH as well as in tissue from glaucomatous patients. There are no qualitative differences. We also demonstrated that astrocytes from the ONH synthesize tropoelastin in vitro. In conclusion, we have demonstrated a tropoelastin alternative splicing pattern in the human optic nerve head and laminar astrocytes. Abnormalities in elastic fibers in the ONH of patients with POAG are not due to an aberrant splice variant of tropoelastin. Astrocytes grown from ONH explants may serve as an in vitro model to study extracellular matrix changes in glaucoma.
弹性纤维是视神经乳头(ONH)细胞外基质的主要成分,在原发性开角型青光眼(POAG)期间会发生显著的形态学变化。先前的研究结果表明,青光眼患者中存在原弹性蛋白mRNA合成的重新激活。在本研究中,我们试图确定人视神经乳头和培养的板层星形胶质细胞中原弹性蛋白的可变剪接模式。此外,我们比较了正常弹性生成的可变剪接模式与原发性开角型青光眼患者弹性蛋白合成重新激活的可变剪接模式。我们的结果表明,原弹性蛋白的外显子23和32在正常视神经乳头以及青光眼患者的组织中均发生可变剪接。不存在质的差异。我们还证明,视神经乳头的星形胶质细胞在体外合成原弹性蛋白。总之,我们已经证明了人视神经乳头和板层星形胶质细胞中原弹性蛋白的可变剪接模式。POAG患者视神经乳头弹性纤维的异常并非由于原弹性蛋白的异常剪接变体所致。从视神经乳头外植体培养的星形胶质细胞可作为研究青光眼细胞外基质变化的体外模型。