Gordon-Thomson C, de Iongh R U, Hales A M, Chamberlain C G, McAvoy J W
Department of Anatomy and Histology and Institute for Biomedical Research (F13), The University of Sydney, NSW, Australia.
Invest Ophthalmol Vis Sci. 1998 Jul;39(8):1399-409.
Transforming growth factor-beta has been shown to induce cataractous changes in rat lenses. This study assesses the relative cataractogenic potential of TGF-beta1, TGF-beta2, and TGF-beta3 and their expression patterns in the rat eye.
Lens epithelial explants and whole lenses from weanling rats were cultured with TGF-beta1, TGF-beta2, or TGF-beta3 at concentrations ranging from 0.025 ng/ml to 4 ng/ml for 3 to 5 days. Cataractous changes were monitored daily by phase contrast microscopy and by immunofluorescent detection of cataract markers alpha-smooth muscle actin and type I collagen. Expression of TGF-beta was studied by immunofluorescence and in situ hybridization on eye sections from neonatal and weanling rats.
All three isoforms induced morphologic changes in lens epithelial explants and cultured lenses that are typically associated with human subcapsular cataract. Transforming growth factor-beta2 and TGF-beta3 were approximately 10 times more potent than TGF-beta1. All three isoforms were expressed in the eye in spatially distinct but overlapping patterns. Transforming growth factor-beta1 and TGF-beta2 and their mRNA were detected in most ocular tissues, including the lens. Although TGF-beta3 was immunolocalized in lens epithelium and fibers and in other ocular tissues, its mRNA was detected only in the retina and choroid.
All three isoforms of TGF-beta are potentially available to lens cells and have the potential to induce cataractous changes. The results suggest that TGF-beta activity is normally tightly regulated in the eye. Activation of TGF-beta in the lens environment, such as may occur during injury, in wound healing, or in pathologic conditions may contribute to cataractogenesis in vivo.
转化生长因子-β已被证明可诱导大鼠晶状体发生白内障样改变。本研究评估了转化生长因子-β1、转化生长因子-β2和转化生长因子-β3的相对致白内障潜力及其在大鼠眼中的表达模式。
将断奶大鼠的晶状体上皮外植体和完整晶状体与浓度范围为0.025 ng/ml至4 ng/ml的转化生长因子-β1、转化生长因子-β2或转化生长因子-β3培养3至5天。每天通过相差显微镜以及白内障标志物α-平滑肌肌动蛋白和I型胶原蛋白的免疫荧光检测来监测白内障样改变。通过免疫荧光和原位杂交对新生和断奶大鼠的眼组织切片研究转化生长因子-β的表达。
所有三种异构体均在晶状体上皮外植体和培养的晶状体中诱导了形态学变化，这些变化通常与人类晶状体后囊下白内障相关。转化生长因子-β2和转化生长因子-β3的效力比转化生长因子-β1高约10倍。所有三种异构体在眼中以空间上不同但重叠的模式表达。在包括晶状体在内的大多数眼组织中检测到转化生长因子-β1和转化生长因子-β2及其mRNA。虽然转化生长因子-β3在晶状体上皮、纤维和其他眼组织中免疫定位，但其mRNA仅在视网膜和脉络膜中检测到。
转化生长因子-β的所有三种异构体都可能作用于晶状体细胞并具有诱导白内障样改变的潜力。结果表明，转化生长因子-β活性在眼中通常受到严格调控。晶状体环境中转化生长因子-β的激活，如在损伤、伤口愈合或病理状况期间可能发生的激活，可能在体内促成白内障的发生。
