Lavker Robert M, Tseng Scheffer C G, Sun Tung-Tien
Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Exp Eye Res. 2004 Mar;78(3):433-46. doi: 10.1016/j.exer.2003.09.008.
Corneal epithelium is traditionally thought to be a self-sufficient, self-renewing tissue implying that its stem cells are located in its basal cell layer. Recent studies indicate however that corneal epithelial stem cells reside in the basal layer of peripheral cornea in the limbal zone, and that corneal and conjunctival epithelia represent distinct cell lineages. These ideas are supported by the unique limbal/corneal expression pattern of the K3 keratin marker for corneal-type differentiation; the restriction of the slow-cycling (label-retaining) cells in the limbus; the distinct keratin expression patterns of corneal and conjunctival epithelial cells even when they are provided with identical in vivo and in vitro growth environments; and the limbal cells' superior ability as compared with central corneal epithelial cells in undergoing in vitro proliferation and in reconstituting in vivo an intact corneal epithelium. The realization that corneal epithelial stem cells reside in the limbal zone provides explanations for several paradoxical properties of corneal epithelium including its 'mature-looking' basal cells, the preponderance of tumor formation in the limbal zone, and the centripetal cellular migration. The limbal stem cell concept has led to a better understanding of the strategies of corneal epithelial repair, to a new classification of various anterior surface epithelial diseases, to the use of limbal stem cells for the reconstruction of corneal epithelium damaged or lost as a consequence of trauma or disease ('limbal stem cell transplantation'), and to the rejection of the traditional notion of 'conjunctival transdifferentiation'. The fact that corneal epithelial stem cells reside outside of the cornea proper suggests that studying corneal epithelium per se without taking into account its limbal zone will yield partial pictures. Future studies need to address the signals that constitute the limbal stem cell niche, the mechanism by which amniotic membrane facilitates limbal stem cell transplantation and ex vivo expansion, and the lineage flexibility of limbal stem cells.
传统观点认为，角膜上皮是一种自给自足、自我更新的组织，这意味着其干细胞位于基底细胞层。然而，最近的研究表明，角膜上皮干细胞存在于角膜缘区周边角膜的基底层，并且角膜上皮和结膜上皮代表不同的细胞谱系。这些观点得到以下几方面的支持：角膜型分化的K3角蛋白标志物在角膜缘/角膜的独特表达模式；角膜缘中慢循环（标记保留）细胞的局限分布；即使在相同的体内和体外生长环境下，角膜和结膜上皮细胞仍具有不同的角蛋白表达模式；与中央角膜上皮细胞相比，角膜缘细胞在体外增殖和体内重建完整角膜上皮方面具有更强的能力。认识到角膜上皮干细胞存在于角膜缘区，为角膜上皮的一些矛盾特性提供了解释，包括其“看似成熟”的基底细胞、角膜缘区肿瘤形成的优势以及细胞向心迁移。角膜缘干细胞概念有助于更好地理解角膜上皮修复策略、对各种眼前表面上皮疾病进行新的分类、利用角膜缘干细胞重建因创伤或疾病而受损或缺失的角膜上皮（“角膜缘干细胞移植”），以及摒弃“结膜转分化”的传统观念。角膜上皮干细胞存在于角膜本身之外这一事实表明，不考虑角膜缘区而单独研究角膜上皮本身将只能得到不完整的情况。未来的研究需要解决构成角膜缘干细胞微环境的信号、羊膜促进角膜缘干细胞移植和体外扩增的机制，以及角膜缘干细胞的谱系灵活性等问题。
