Symonds Joel G, Lovicu Frank J, Chamberlain Coral G
Discipline of Anatomy and Histology and Institute for Biomedical Research (F13), University of Sydney, Sydney, NSW 2006, Australia.
Exp Eye Res. 2006 Apr;82(4):693-9. doi: 10.1016/j.exer.2005.09.008. Epub 2005 Dec 15.
Following cataract surgery, many patients suffer secondary loss of vision because of posterior capsule opacification (PCO), which arises when residual lens epithelial cells become aberrant and migrate into the light path. Transforming growth factor-beta (TGFbeta)-induced transdifferentiation of lens cells appears to play a key role in this process. Fibroblast growth factor (FGF) may also play a role by promoting the survival of TGFbeta-affected cells and influencing their subsequent behaviour. In the present study, the effects of two different TGFbeta and FGF treatment regimes were compared in rat lens epithelial explants with either low or high initial cell coverage. Explants treated with 50 pg ml(-1) TGFbeta2 and 20 ng ml(-1) FGF-2 sequentially (day 0, day 1) or simultaneously (day 0), then cultured for up to 30 days with FGF, were assessed by light microscopy and immunolocalisation of markers for transdifferentiation (alpha-smooth muscle actin (alphaSMA) and type I collagen) or lens epithelial phenotype (Pax6) and fibre differentiation (beta-crystallin). By day 4, most cells had lost Pax6 reactivity, alphaSMA reactivity was evident, and there were differences between growth factor treatment groups, low and high initial cell coverage explants, and peripheral and central regions of explants. On day 30 of culture, all explants were well populated with cells, irrespective of treatment and initial cell coverage, and exhibited diverse PCO-like morphological changes, with expression of transdifferentiation markers and beta-crystallin in virtually all cells. Such overall resilience to variations in conditions may contribute to the insidious nature of PCO, while factors related to observed early differences between groups may contribute to PCO pleiomorphism.
白内障手术后，许多患者会因后囊膜混浊（PCO）而继发视力丧失，后囊膜混浊是在残留的晶状体上皮细胞发生异常并迁移到光路中时出现的。转化生长因子-β（TGFβ）诱导的晶状体细胞转分化似乎在这一过程中起关键作用。成纤维细胞生长因子（FGF）可能也通过促进受TGFβ影响的细胞存活并影响其后续行为而发挥作用。在本研究中，比较了两种不同的TGFβ和FGF处理方案对初始细胞覆盖率低或高的大鼠晶状体上皮外植体的影响。用50 pg/ml TGFβ2和20 ng/ml FGF-2依次（第0天、第1天）或同时（第0天）处理外植体，然后用FGF培养长达30天，通过光学显微镜以及对转分化标志物（α-平滑肌肌动蛋白（αSMA）和I型胶原蛋白）或晶状体上皮表型（Pax6）和纤维分化（β-晶状体蛋白）进行免疫定位来评估。到第4天时，大多数细胞失去了Pax6反应性，αSMA反应性明显，并且生长因子处理组、初始细胞覆盖率低和高的外植体以及外植体的周边和中央区域之间存在差异。在培养的第30天，所有外植体都有大量细胞，无论处理方式和初始细胞覆盖率如何，并且表现出各种类似PCO的形态变化，几乎所有细胞中都有转分化标志物和β-晶状体蛋白的表达。这种对条件变化的总体适应能力可能导致PCO的隐匿性，而与观察到的组间早期差异相关的因素可能导致PCO的多形性。
