Marcantonio J M, Syam P P, Liu C S C, Duncan G
School of Biological Sciences, University of East Anglia, NR4 7TJ, Norwich, UK.
Exp Eye Res. 2003 Sep;77(3):339-46. doi: 10.1016/s0014-4835(03)00125-8.
Anterior subcapsular cataracts cause a serious loss of vision and are normally associated with ocular trauma, inflammation or clinical skin conditions. They appear to be accompanied by epithelial cell growth and transdifferentiation where unscheduled production of a number of proteins, including alpha smooth muscle actin (alpha-sma), occurs. Clinical studies have also revealed an up-regulation of the TGFbeta signalling pathway in such cataracts. The present study, using phase contrast and immunofluorescent techniques, was undertaken to investigate the extent of alpha-sma expression in traumatic cataracts, in capsulorhexis specimens obtained during cataract surgery and in aged human lenses from donor eyes. The donor lenses were also exposed to trauma or TGFbeta in culture to observe their relative contribution to alpha-sma production. Dense anterior subcapsular cataracts were relatively rare (<1%), but all showed a pronounced up-regulation of alpha-sma, which was located both in anterior cells of normal appearance and in nucleated fibroblastic cells lying beneath the anterior epithelium. Surprisingly, more than 50% of capsulorhexis specimens from mature cataracts showed expression of alpha-sma, although to a limited extent. Alpha-sma was not expressed in any of the clear donor lenses and culture for 8 days in EMEM did not induce expression. Interestingly, unlike their young animal counterparts, human lenses failed to show the presence of alpha-sma when exposed to 10 ng ml(-1) TGFbeta. However, after culture, lenses with pre-existing cortical opacities did express alpha-sma, as did clear lenses subjected to injury or trauma. It appears that the greater the stress, the greater is the expression of alpha-sma. Cataract, and especially cortical cataract, should therefore be seen as associated with stress-induced signalling pathways in the lens that lead to the transdifferentiation of the anterior epithelial cells.
前囊下白内障会导致严重的视力丧失，通常与眼外伤、炎症或临床皮肤疾病有关。它们似乎伴随着上皮细胞的生长和转分化，在此过程中会出现一些蛋白质的异常产生，包括α平滑肌肌动蛋白（α-sma）。临床研究还表明，此类白内障中TGFβ信号通路上调。本研究采用相差显微镜和免疫荧光技术，旨在研究α-sma在创伤性白内障、白内障手术中获取的撕囊标本以及供体眼的老年人类晶状体中的表达程度。还将供体晶状体在培养中暴露于创伤或TGFβ，以观察它们对α-sma产生的相对作用。致密的前囊下白内障相对少见（<1%），但均显示α-sma明显上调，其位于外观正常的前细胞以及前上皮下方的有核成纤维细胞中。令人惊讶的是，超过50%的成熟白内障撕囊标本显示α-sma表达，尽管程度有限。透明的供体晶状体中均未表达α-sma，在伊格尔最低限度必需培养基（EMEM）中培养8天也未诱导表达。有趣的是，与幼龄动物不同，人类晶状体在暴露于10 ng ml(-1) TGFβ时未显示α-sma的存在。然而，培养后，已有皮质混浊的晶状体确实表达了α-sma，遭受损伤或创伤的透明晶状体也是如此。似乎压力越大，α-sma的表达就越高。因此，白内障，尤其是皮质性白内障，应被视为与晶状体中应激诱导的信号通路相关，该通路导致前上皮细胞转分化。
