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Primary cilia in corneal development and disease

Ting Song Jun Zhou

Ting Song, Jun Zhou. Primary cilia in corneal development and disease. Zoological Research, 2020, 41(5): 495-502. doi: 10.24272/j.issn.2095-8137.2020.109
Citation: Ting Song, Jun Zhou. Primary cilia in corneal development and disease. Zoological Research, 2020, 41(5): 495-502. doi: 10.24272/j.issn.2095-8137.2020.109


doi: 10.24272/j.issn.2095-8137.2020.109

Primary cilia in corneal development and disease

Funds: This work was supported by the Taishan Scholars Program of Shandong Province (20161201)
More Information
  • 摘要: 角膜是位于眼球前部的透明的无血管组织,是防止外部损伤的重要屏障。角膜的上皮细胞和内皮细胞都具有原生纤毛,它们可以感知外部环境的变化并调节细胞内信号通路。越来越多的证据表明,原生纤毛以多种方式调节角膜的发育,包括参与角膜上皮分层和维持角膜内皮细胞形态。此外,原生纤毛也参与了角膜疾病的发病过程。在这篇综述中,我们讨论了原生纤毛与角膜发育近年来的报道,明确了原生纤毛在角膜发育中的关键作用。同时我们还讨论了纤毛功能异常和角膜疾病之间的联系,为靶向原生纤毛来治疗角膜疾病提供依据。
  • Figure  1.  Structures of normal and diseased corneal tissues

    The cornea is composed of an epithelial layer, stroma, endothelial layer, Bowman’s membrane, and Descemet’s membrane. The epithelial layer is formed from multiple layers of cells, but only basal layer cells can divide. The endothelial layer is a monolayer and the cells are blocked in the G0/G1 phase of the cell cycle. In the normal cornea, the epithelial layer relies on a stable multilayered structure to prevent external damage, and endothelial cells are closely arranged together with Descemet’s membrane to prevent the flow of aqueous humor to the stroma and consequent corneal edema. Keratoconus is the most common corneal epithelial disease and is characterized by protrusion of the central cornea and thinning of the epithelial layer. Some abnormally expressed cilium-related molecules have been identified in keratoconus, such as up-regulation of TGF-β1 and TIMP3 (negatively correlated with cilia) and down-regulation of VEGF, COL1A1, and COL1A2 (positively correlated with cilia). Endothelial dystrophy is the most common retinal endothelial disease, in which endothelial cells are lost in large quantities, cells expand, and Descemet’s membrane is destroyed, causing aqueous humor to flow to the stroma, leading to corneal edema. Some abnormal cilium-related molecules have also been found in endothelial dystrophy, such as down-regulated ZEB1 expression, which is positively correlated with cilia, and TCF4 mutations that affect the Wnt/β-catenin pathway.

    Figure  2.  Patterns of primary cilia during corneal development

    A: In mice, at E11, the epithelial layer begins to develop from the ectoderm; at E12.5, the epithelial layer continues to form, at which time primary cilia can be detected; at E17.5, the epithelial layer slowly develops into two layers until the mouse opens its eyelids (around P12), after which it begins to develop rapidly. By P70, the epithelial layer matures, forming a stable structure of 6−8 layers of cells. Throughout development, primary cilia only exist on basal cells. B: At E11-12.5, neural crest cells begin to migrate to form endothelial cells; at E17.5, tight junctions form between the cells. Primary cilia are not detectable throughout the embryonic period, and cell morphology is irregular. From P2 to P12, the primary cilia begin to grow, regulating hexagonal cell morphology changes; at P35, most of the primary cilia depolymerize. By P70, the primary cilia completely disappear, cells are regular hexagons, and a mature endothelial layer has developed.

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  • 收稿日期:  2020-05-06
  • 录用日期:  2020-07-17
  • 网络出版日期:  2020-08-04
  • 刊出日期:  2020-09-18