From the Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan.
Cornea. 2010 Nov;29 Suppl 1:S52-6. doi: 10.1097/ICO.0b013e3181efe36a.
A single layer of corneal endothelial cells covers the posterior surface of the Descemet membrane. Normally, corneal endothelial cells do not proliferate, suggesting that factors inhibit their undergoing mitosis. Fibroblastic transformation of corneal endothelial cells due to syphilitic interstitial keratitis or alkali burn may result in stromal opacification. Various growth factors such as fibroblast growth factor 2 and transforming growth factor β are involved in "endothelial-mesenchymal transition (EnMT)." Endothelial wound-healing assay experiments revealed that cell migration toward artificial wound defect was mediated by p38 and c-Jun N-terminal kinase. To understand whether Smad signal might have an important role in EnMT regulation, gene transfer of Smad7 was employed to block transforming growth factor β/Smad signal in rat corneal endothelium 3 days before alkali burning. EnMT during healing interval after alkali burn was markedly suppressed by Smad7 overexpression associated with upregulation of cell proliferation. Therefore, blocking Smad signal effectively suppresses injury-induced EnMT and fibrogenic reaction by corneal endothelium without impairing repair of wound defect. Strategies that block Smad may be useful for prevention and treatment of fibrogenic disorders in the corneal endothelium.
一层角膜内皮细胞覆盖在后弹力膜的表面。正常情况下，角膜内皮细胞不会增殖，这表明有某些因素抑制了它们的有丝分裂。梅毒性间质性角膜炎或碱烧伤导致的角膜内皮细胞成纤维样转化，可能导致基质混浊。成纤维细胞生长因子 2 和转化生长因子 β 等各种生长因子参与“内皮-间充质转化（EnMT）”。内皮细胞创伤愈合试验表明，p38 和 c-Jun N 末端激酶介导细胞向人工创伤缺陷的迁移。为了了解 Smad 信号是否在 EnMT 调控中具有重要作用，在碱烧伤前 3 天通过基因转染 Smad7 阻断转化生长因子 β/Smad 信号，从而抑制大鼠角膜内皮中的 EnMT。与细胞增殖上调相关，Smad7 过表达显著抑制碱烧伤后愈合期间的 EnMT 和纤维生成反应。因此，阻断 Smad 信号可有效抑制损伤诱导的角膜内皮 EnMT 和纤维生成反应，而不损害创伤缺陷的修复。阻断 Smad 的策略可能有助于预防和治疗角膜内皮的纤维生成性疾病。
