Pena J D, Taylor A W, Ricard C S, Vidal I, Hernandez M R
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis 63110, USA.
Br J Ophthalmol. 1999 Feb;83(2):209-18. doi: 10.1136/bjo.83.2.209.
To determine if the isoforms of transforming growth factor beta (TGF-beta) are present in fetal, normal adult, and glaucomatous optic nerve heads.
To localise cells synthesising TGF-beta, optic nerve heads were stained using antibodies to TGF-beta 1, TGF-beta 2, and TGF-beta 3. To demonstrate synthesis, human optic nerve heads from fetal, glaucomatous, and normal age matched subjects were explanted, cultured overnight, and the culture supernatant was assayed for the presence of TGF-beta 1 and TGF-beta 2 by bioassay. In addition, semiquantitative RT-PCR was performed to determine the gene expression pattern of TGF-beta 2.
Immunohistochemistry of glaucomatous samples revealed the presence of intense staining for TGF-beta 2 primarily in astrocytes, whereas TGF-beta 1 was localised to blood vessels. No TGF-beta 3 immunoreactivity was observed. There was little or no expression of TGF-beta in normal optic nerve heads. Optic nerve heads from glaucomatous eyes released 70-100-fold more TGF-beta 2 than normal age matched optic nerve heads. Fetal optic nerve heads released 90-100-fold more TGF-beta 2 than normal adult optic nerve heads. TGF-beta 1 was undetectable by bioassay in all samples tested. There was no apparent increase in TGF-beta 2 gene expression in glaucomatous and fetal eyes, suggesting post-transcriptional regulatory mechanisms.
These results demonstrate that TGF-beta 2 is produced in high levels in the fetal and glaucomatous optic nerve heads, perhaps by a mechanism of post-transcriptional regulation. TGF-beta may be important during development of the optic nerve head and, in glaucoma, TGF-beta 2 may be a mediator of astrocyte reactivation and extracellular matrix remodelling in the lamina cribrosa.
确定转化生长因子β（TGF-β）的异构体是否存在于胎儿、正常成人及青光眼性视神经乳头中。
为定位合成TGF-β的细胞，使用抗TGF-β 1、TGF-β 2和TGF-β 3抗体对视神经乳头进行染色。为证明合成情况，将来自胎儿、青光眼患者及年龄匹配的正常受试者的人视神经乳头取出，培养过夜，并用生物测定法检测培养上清液中TGF-β 1和TGF-β 2的存在情况。此外，进行半定量逆转录聚合酶链反应（RT-PCR）以确定TGF-β 2的基因表达模式。
青光眼样本的免疫组织化学显示，TGF-β 2主要在星形胶质细胞中呈强染色，而TGF-β 1定位于血管。未观察到TGF-β 3免疫反应性。正常视神经乳头中TGF-β的表达很少或没有。青光眼性眼的视神经乳头释放的TGF-β 2比年龄匹配的正常视神经乳头多70 - 100倍。胎儿视神经乳头释放的TGF-β 2比正常成人视神经乳头多90 - 100倍。在所有测试样本中，生物测定法均未检测到TGF-β 1。青光眼和胎儿眼中TGF-β 2基因表达没有明显增加，提示存在转录后调控机制。
这些结果表明，TGF-β 2在胎儿和青光眼性视神经乳头中高水平产生，可能是通过转录后调控机制。TGF-β在视神经乳头发育过程中可能很重要，在青光眼中，TGF-β 2可能是筛板中星形胶质细胞再激活和细胞外基质重塑的介质。
